The high mobility group A1 (HMGA1) transcriptome in cancer and development

Current Molecular Medicine

Volumn 16, Issue 4, 2016, Pages 353-393

  Sumter, T F ^a   Xian, L ^b   Huso, T ^b   Koo, M ^b   Chang, Y T ^b   Almasri, T N ^b   Chia, L ^b   Inglis, C ^a   Reid, D ^a   Resar, L M S ^b  

^a WINTHROP UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cancer; Cancer stem cells; Chromatin; Embryonic stem cells; Genes; High mobility group A1; HMGA; Metastasis; Tumor progression

Indexed keywords

BETA INTERFERON; CD8BETA1 ANTIGEN; CHEMOKINE RECEPTOR CXCR3; CXCL1 CHEMOKINE; CYTOCHROME B 245 PROTEIN; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; GAMMA INTERFERON; GRANZYME M; HIGH MOBILITY GROUP A PROTEIN; IMMUNOGLOBULIN HEAVY CHAIN EPSILON; IMMUNOGLOBULIN HEAVY CHAIN MU; INTERLEUKIN 10; INTERLEUKIN 15; INTERLEUKIN 15 RECEPTOR ALPHA; INTERLEUKIN 18 RECEPTOR ALPHA; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR BETA; INTERLEUKIN 4; LUNG KRUPPLE LIKE FACTOR; LYMPHOTOXIN; MEMBRANE PROTEIN; PADGEM PROTEIN; PEPTIDES AND PROTEINS; PROTEIN KINASE SYK; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR GATA 4; TRANSCRIPTION FACTOR GATA 6; TRANSCRIPTOME; UNCLASSIFIED DRUG; HIGH MOBILITY GROUP A1A PROTEIN;

ADIPOGENESIS; ADULT STEM CELL; ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; CANCER CELL; CANCER PROGNOSIS; CARCINOGENESIS; CELL PROLIFERATION; CELL STRUCTURE; CHROMATIN ASSEMBLY AND DISASSEMBLY; EMBRYO DEVELOPMENT; EXTRACELLULAR MATRIX; GENE OVEREXPRESSION; GENETIC TRANSFORMATION; HUMAN; INTRACELLULAR SIGNALING; METABOLISM; METASTASIS; MITOCHONDRION; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLURIPOTENT STEM CELL; REGULATORY MECHANISM; UPREGULATION; VASCULAR SMOOTH MUSCLE; WALKER WARBURG SYNDROME; ANIMAL; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; GROWTH, DEVELOPMENT AND AGING;

ANIMALS; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; GROWTH AND DEVELOPMENT; HMGA1A PROTEIN; HUMANS; NEOPLASMS; PLURIPOTENT STEM CELLS; TRANSCRIPTOME;

EID: 84964241042     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/1566524016666160316152147     Document Type: Article

References (297)

1. Goodwin G, Walker JH, Johns EW. The high mobility group (HMG) nonhistone chromosomal proteins. The cell nucleus. New York: Academic Press; 1978. pp. 181-219.
2. Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem 1973; 38: 14-9.
3. Lund T, Holtlund J, Fredriksen M, Laland SG. On the presence of two new high mobility group-like proteins in Hela S3 cells. FEBS Lett 1983; 152: 163-7.
4. Giancotti V, Berlingieri MT, DiFiore PP, Fusco A, Vecchio G, Crane-Robinson C. Changes in nuclear proteins on transformation of rat epithelial thyroid cells by a murine sarcoma retrovirus. Cancer Res 1985; 45: 6051-7.
5. Giancotti V, Pani B, D'Andrea P, et al. Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle t genes. EMBO J. 1987; 6: 1981-7.
6. Johnson KR, Lehn DA, Elton TS, Barr PJ, Reeves R. Complete murine cdna sequence, genomic structure, and tissue expression of the high mobility group protein HMGI(Y). J Biol Chem 1988; 263: 18338-42.
7. Friedmann M, Holth LT, Zoghbi HY, Reeves R. Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene. Nucleic Acids Res 1993; 21: 4259-67.
8. Giancotti V, Buratti E, Perissin L, et al. Analysis of the HMGI nuclear proteins in mouse neoplastic cells induced by different procedures. Exp Cell Res 1989; 184: 538-45.
9. Bustin M, Lehn DA, Landsman D. Structural features of the hmg chromosomal proteins and their genes. Biochim Biophys Acta 1990; 1049: 231-43.
10. Giancotti V, Bandiera A, Buratti E, et al. Comparison of multiple forms of the high mobility group I proteins in rodent and human cells. Identification of the human High Mobility Group I-C protein. Eur J Biochem 1991; 198: 211-6.
11. Manfioletti G, Rustighi A, Mantovani F, Goodwin GH, Giancotti V. Isolation and characterization of the gene coding for murine high-mobility-group protein HMGI-C. Gene 1995; 167: 249-53.
12. Manfioletti G, Giancotti V, Bandiera A, et al. cDNA cloning of the HMGI-C phosphoprotein, a nuclear protein associated with neoplastic and undifferentiated phenotypes. Nucleic Acids Res 1991; 19: 6793-7.
13. Solomon MJ, Strauss F, Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A 1986; 83: 1276-80.
14. Reeves R, Nissen MS. The AT-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem 1990; 265: 8573-82.
15. Geierstanger BH, Volkman BF, Kremer W, Wemmer DE. Short peptide fragments derived from HMG-I/Y proteins bind specifically to the minor groove of DNA. Biochemistry 1994; 33: 5347-55.
16. Maher JF, Nathans D. Multivalent DNA-binding properties of the HMG-1 proteins. Proc Natl Acad Sci U S A 1996; 93: 6716-20.
17. Bustin M, Reeves R. High-mobility-group chromosomal proteins: Architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol 1996; 54: 35-100.
18. Banks GC, Mohr B, Reeves R. The HMG-I(Y) AT-hook peptide motif confers DNA-binding specificity to a structured chimeric protein. J Biol Chem 1999; 274: 16536-44.
19. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol 1999; 19: 5237-46.
20. Reeves R, Beckerbauer L. HMGI/Y proteins: Flexible regulators of transcription and chromatin structure. Biochim Biophys Acta 2001; 1519: 13-29.
21. Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol 2007; 17: 72-9.
22. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer 2007; 7: 899-910.
23. Resar LM. The high mobility group A1 gene: Transforming inflammatory signals into cancer? Cancer Res 2010; 70: 436-9.
24. Shah SN, Resar LM. High mobility group A1 and cancer: Potential biomarker and therapeutic target. Histol Histopathol 2012; 27: 567-79.
25. Di Cello F, Hillion J, Hristov A, et al. HMGA2 participates in transformation in human lung cancer. Mol Cancer Res 2008; 6: 743-50.
26. Hristov AC, Cope L, Reyes MD, et al. HMGA2 protein expression correlates with lymph node metastasis and increased tumor grade in pancreatic ductal adenocarcinoma. Mod Pathol 2009; 22: 43-9.
27. Resar LM, Brodsky RA. "Let"-ing go with clonal expansion? Blood. 2011; 117: 5788-90.
28. Wood LJ, Maher JF, Bunton TE, Resar LM. The oncogenic properties of the HMG-I gene family. Cancer Res 2000; 60: 4256-61.
29. Reeves R, Edberg DD, Li Y. Architectural transcription factor HMGI(Y) promotes tumor progression and mesenchymal transition of human epithelial cells. Mol Cell Biol 2001; 21: 575-94.
30. Reeves R. Molecular biology of HMGA proteins: Hubs of nuclear function. Gene 2001; 277: 63-81.
31. Moliterno AR, Resar LM. AKNA: Another AT-hook transcription factor "hooking-up" with inflammation. Cell Res 2011; 21: 1528-30.
32. Dement GA, Treff NR, Magnuson NS, Franceschi V, Reeves R. Dynamic mitochondrial localization of nuclear transcription factor HMGA1. Exp Cell Res 2005; 307: 388-401.
33. Dement GA, Maloney SC, Reeves R. Nuclear HMGA1 nonhistone chromatin proteins directly influence mitochondrial transcription, maintenance, and function. Exp Cell Res 2007; 313: 77-87.
34. Mao L, Wertzler KJ, Maloney SC, Wang Z, Magnuson NS, Reeves R. HMGA1 levels influence mitochondrial function and mitochondrial DNA repair efficiency. Mol Cell Biol 2009; 29: 5426-40.
35. Foti D, Chiefari E, Fedele M, et al. Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice. Nat Med 2005; 11: 765-73.
36. Chiefari E, Paonessa F, Iiritano S, et al. The cAMP-HMGA1- RBP4 system: A novel biochemical pathway for modulating glucose homeostasis. BMC Biol 2009; 7: 24.
37. Chiefari E, Iiritano S, Paonessa F, et al. Pseudogenemediated posttranscriptional silencing HMGA1 can result in insulin resistance and type 2 diabetes. Nat Commun 2010; 1: 1-7.
38. Semple RK. From bending DNA to diabetes: The curious case of HMGA1. J Biol 2009; 8: 64.
39. Manabe T, Katayama T, Sato N, et al. Induced HMGA1a expression causes aberrant splicing of presenilin-2 premRNA in sporadic alzheimer's disease. Cell Death Differ 2003; 10: 698-708.
40. Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M. Induction of neuronal death by ER stress in alzheimer's disease. J Chem Neuroanat 2004; 28: 67-78.
41. Manabe T, Ohe K, Katayama T, et al. HMGA1a: Sequencespecific RNA-binding factor causing sporadic alzheimer's disease-linked exon skipping of presenilin-2 pre-mRNA. Genes Cells 2007; 12: 1179-91.
42. Ohe K, Mayeda A. HMGA1a trapping of u1 snrnp at an authentic 5' splice site induces aberrant exon skipping in sporadic Alzheimer's disease. Mol Cell Biol 2010; 30: 2220-8.
43. Giancotti V, Bandiera A, Ciani L, et al. High-mobility-group (HMG) proteins and histone h1 subtypes expression in normal and tumor tissues of mouse. Eur J Biochem 1993; 213: 825-32.
44. Lanahan A, Williams JB, Sanders LK, Nathans D. Growth factor-induced delayed early response genes. Mol Cell Biol 1992; 12: 3919-29.
45. Chiappetta G, Tallini G, De Biasio MC, et al. Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma. Cancer Res 1998; 58: 4193-8.
46. Chiappetta G, Bandiera A, Berlingieri MT, et al. The expression of the high mobility group HMGI (Y) proteins correlates with the malignant phenotype of human thyroid neoplasias. Oncogene 1995; 10: 1307-14.
47. Dal Cin P, Fusco A, Belge G, et al. Involvement of the HMGI(Y) gene in a microfollicular adenoma of the thyroid. Genes Chromosomes Cancer 1999; 24: 286-9.
48. Czyz W, Balcerczak E, Jakubiak M, Pasieka Z, Kuzdak K, Mirowski M. Hmgi(y) gene expression as a potential marker of thyroid follicular carcinoma. Langenbecks Arch Surg 2004; 389: 193-7.
49. Sarhadi VK, Wikman H, Salmenkivi K, et al. Increased expression of high mobility group A proteins in lung cancer. J Pathol 2006; 209: 206-12.
50. Hillion J, Wood LJ, Mukherjee M, et al. Upregulation of MMP- 2 by HMGA1 promotes transformation in undifferentiated, large-cell lung cancer. Mol Cancer Res 2009; 7: 1803-12.
51. Kettunen E, Anttila S, Seppanen JK, et al. Differentially expressed genes in nonsmall cell lung cancer: Expression profiling of cancer-related genes in squamous cell lung cancer. Cancer Genet Cytogenet 2004; 149: 98-106.
52. Holth LT, Thorlacius AE, Reeves R. Effects of epidermal growth factor and estrogen on the regulation of the HMG-I/Y gene in human mammary epithelial cell lines. DNA Cell Biol 1997; 16: 1299-309.
53. Liu WM, Guerra-Vladusic FK, Kurakata S, Lupu R, Kohwi-Shigematsu T. HMG-I(Y) recognizes base-unpairing regions of matrix attachment sequences and its increased expression is directly linked to metastatic breast cancer phenotype. Cancer Res 1999; 59: 5695-703.
54. Dolde CE, Mukherjee M, Cho C, Resar LM. HMG-I/Y in human breast cancer cell lines. Breast Cancer Res Treat 2002; 71: 181-91.
55. Flohr AM, Rogalla P, Bonk U, et al. High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade. Histol Histopathol 2003; 18: 999-1004.
56. Chiappetta G, Botti G, Monaco M, et al. HMGA1 protein overexpression in human breast carcinomas: Correlation with erbb2 expression. Clin Cancer Res 2004; 10: 7637-44.
57. Zou Y, Wang Y. Mass spectrometric analysis of high-mobility group proteins and their post-translational modifications in normal and cancerous human breast tissues. J Proteome Res 2007; 6: 2304-14.
58. Ben-Porath I, Thomson MW, Carey VJ, et al. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008; 40: 499-507.
59. Chiappetta G, Ottaiano A, Vuttariello E, et al. HMGA1 protein expression in familial breast carcinoma patients. Eur J Cancer 2010; 46: 332-9.
60. Takaha N, Resar LM, Vindivich D, Coffey DS. High mobility group protein HMGI(Y) enhances tumor cell growth, invasion, and matrix metalloproteinase-2 expression in prostate cancer cells. Prostate 2004; 60: 160-7.
61. Takaha N, Hawkins AL, Griffin CA, Isaacs WB, Coffey DS. High mobility group protein I(Y): A candidate architectural protein for chromosomal rearrangements in prostate cancer cells. Cancer Res 2002; 62: 647-51.
62. Takeuchi I, Takaha N, Nakamura T, et al. High mobility group protein at-hook 1 (HMGA1) is associated with the development of androgen independence in prostate cancer cells. Prostate 2012; 72: 1124-32.
63. Fedele M, Bandiera A, Chiappetta G, et al. Human colorectal carcinomas express high levels of high mobility group HMGI (Y) proteins. Cancer Res 1996; 56: 1896-901.
64. Kim DH, Park YS, Park CJ, et al. Expression of the HMGI(Y) gene in human colorectal cancer. Int J Cancer 1999; 84: 376-80.
65. Chiappetta G, Manfioletti G, Pentimalli F, et al. High mobility group HMGI(Y) protein expression in human colorectal hyperplastic and neoplastic diseases. Int J Cancer 2001; 91: 147-51.
66. Cleynen I, Huysmans C, Sasazuki T, Shirasawa S, Van de Ven W, Peeters K. Transcriptional control of the human high mobility group a1 gene: Basal and oncogenic ras-regulated expression. Cancer Res 2007; 67: 4620-9.
67. Grade M, Hormann P, Becker S, et al. Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas. Cancer Res 2007; 67: 41-56.
68. Belton A, Gabrovsky A, Bae YK, et al. HMGA1 induces intestinal polyposis in transgenic mice and drives tumor progression and stem cell properties in colon cancer cells. PLoS One 2012; 7: e30034.
69. Abe N, Watanabe T, Masaki T, et al. Pancreatic duct cell carcinomas express high levels of high mobility group I(Y) proteins. Cancer Res 2000; 60: 3117-22.
70. Liau SS, Jazag A, Whang EE. HMGA1 is a determinant of cellular invasiveness and in vivo metastatic potential in pancreatic adenocarcinoma. Cancer Res 2006; 66: 11613-22.
71. Liau SS, Jazag A, Ito K, Whang EE. Overexpression of HMGA1 promotes anoikis resistance and constitutive akt activation in pancreatic adenocarcinoma cells. Br J Cancer 2007; 96: 993-1000.
72. Liau SS, Rocha F, Matros E, Redston M, Whang E. High mobility group at-hook 1 (HMGA1) is an independent prognostic factor and novel therapeutic target in pancreatic adenocarcinoma. Cancer 2008; 113: 302-14.
73. Liau SS, Whang E. Hmga1 is a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma. Clin Cancer Res 2008; 14: 1470-7.
74. Hristov AC, Cope L, Di Cello F, et al. HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma. Mod Pathol 2010; 23: 98-104.
75. Tesfaye A, Di Cello F, Hillion J, et al. The high-mobility group A1 gene up-regulates cyclooxygenase 2 expression in uterine tumorigenesis. Cancer Res 2007; 67: 3998-4004.
76. Bandiera A, Bonifacio D, Manfioletti G, et al. Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix. Cancer Res 1998; 58: 426-31.
77. Takaha N, Sowa Y, Takeuchi I, Hongo F, Kawauchi A, Miki T. Expression and role of HMGA1 in renal cell carcinoma. J Urol 2012; 187: 2215-22.
78. Rho YS, Lim YC, Park IS, et al. High mobility group HMGI(Y) protein expression in head and neck squamous cell carcinoma. Acta Otolaryngol 2007; 127: 76-81.
79. Pomeroy SL, Tamayo P, Gaasenbeek M, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 2002; 415: 436-42.
80. Giannini G, Cerignoli F, Mellone M, et al. High mobility group A1 is a molecular target for MYCN in human neuroblastoma. Cancer Res 2005; 65: 8308-16.
81. Giannini G, Cerignoli F, Mellone M, et al. Molecular mechanism of HMGA1 deregulation in human neuroblastoma. Cancer Lett 2005; 228: 97-104.
82. Cerignoli F, Ambrosi C, Mellone M, et al. HMGA molecules in neuroblastic tumors. Ann N Y Acad Sci 2004; 1028: 122-32.
83. Giannini G, Kim CJ, Di Marcotullio L, et al. Expression of the HMGI(Y) gene products in human neuroblastic tumours correlates with differentiation status. Br J Cancer 2000; 83: 1503-9.
84. Giannini G, Di Marcotullio L, Ristori E, et al. HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness. Cancer Res 1999; 59: 2484-92.
85. Rahman MM, Qian ZR, Wang EL, et al. Frequent overexpression of hmga1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation. Br J Cancer 2009; 100: 501-10.
86. Akaboshi S, Watanabe S, Hino Y, et al. HMGA1 is induced by wnt/beta-catenin pathway and maintains cell proliferation in gastric cancer. Am J Pathol 2009; 175: 1675-85.
87. Chuma M, Saeki N, Yamamoto Y, et al. Expression profiling in hepatocellular carcinoma with intrahepatic metastasis: Identification of high-mobility group I(Y) protein as a molecular marker of hepatocellular carcinoma metastasis. Keio J Med 2004; 53: 90-7.
88. Wood LJ, Mukherjee M, Dolde CE, et al. HMG-I/Y, a new cmyc target gene and potential oncogene. Mol Cell Biol 2000; 20: 5490-502.
89. Pierantoni GM, Agosti V, Fedele M, et al. High-mobility group A1 proteins are overexpressed in human leukaemias. Biochem J 2003; 372: 145-50.
90. Xu Y, Sumter TF, Bhattacharya R, et al. The HMG-I oncogene causes highly penetrant, aggressive lymphoid malignancy in transgenic mice and is overexpressed in human leukemia. Cancer Res 2004; 64: 3371-5.
91. Hillion J, Dhara S, Sumter TF, et al. The high-mobility group A1a/signal transducer and activator of transcription-3 axis: An achilles heel for hematopoietic malignancies? Cancer Res 2008; 68: 10121-7.
92. Karp JE, Smith BD, Resar LS, et al. Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias. Blood. 2011; 117: 3302-10.
93. Nelson DM, Joseph B, Hillion J, Segal J, Karp JE, Resar LM. Flavopiridol induces bcl-2 expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia. Leuk Lymphoma 2011; 52: 1999-2006.
94. Tarbe N, Evtimova V, Burtscher H, Jarsch M, Alves F, Weidle UH. Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasisassociated genes. Anticancer Res 2001; 21: 3221-8.
95. Chiappetta G, Avantaggiato V, Visconti R, et al. High level expression of the HMGI (Y) gene during embryonic development. Oncogene 1996; 13: 2439-46.
96. Zhou G, Chen J, Lee S, Clark T, Rowley JD, Wang SM. The pattern of gene expression in human CD34(+) stem/progenitor cells. Proc Natl Acad Sci U S A 2001; 98: 13966-71.
97. Chou BK, Mali P, Huang X, et al. Efficient human ips cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res 2011; 21: 518-29.
98. Shah SN, Kerr C, Cope L, et al. HMGA1 reprograms somatic cells into pluripotent stem cells by inducing stem cell transcriptional networks. PLoS One 2012; 7: e48533
99. Somervaille TC, Matheny CJ, Spencer GJ, et al. Hierarchical maintenance of mll myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells. Cell Stem Cell 2009; 4: 129-40.
100. Fedele M, Pentimalli F, Baldassarre G, et al. Transgenic mice overexpressing the wild-type form of the HMGA1 gene develop mixed growth hormone/prolactin cell pituitary adenomas and natural killer cell lymphomas. Oncogene 2005; 24: 3427-35.
101. Fedele M, Fusco A. Role of the high mobility group A proteins in the regulation of pituitary cell cycle. J Mol Endocrinol 2010; 44: 309-18.
102. Rothermund K, Rogulski K, Fernandes E, et al. C-mycindependent restoration of multiple phenotypes by two c-myc target genes with overlapping functions. Cancer Res 2005; 65: 2097-107.
103. Pierantoni GM, Battista S, Pentimalli F, et al. A truncated HMGA1 gene induces proliferation of the 3T3-L1 preadipocytic cells: A model of human lipomas. Carcinogenesis 2003; 24: 1861-9.
104. Pierantoni GM, Fedele M, Pentimalli F, et al. High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein which inhibits cell growth. Oncogene 2001; 20: 6132-41.
105. Fedele M, Pierantoni GM, Berlingieri MT, et al. Overexpression of proteins HMGA1 induces cell cycle deregulation and apoptosis in normal rat thyroid cells. Cancer Res 2001; 61: 4583-90.
106. Reeves R, Nissen MS. Cell cycle regulation and functions of HMG-I(Y). Prog Cell Cycle Res 1995; 1: 339-49.
107. Kolb S, Fritsch R, Saur D, Reichert M, Schmid RM, Schneider G. HMGA1 controls transcription of insulin receptor to regulate cyclin D1 translation in pancreatic cancer cells. Cancer Res 2007; 67: 4679-86.
108. Schuldenfrei A, Belton A, Kowalski J, et al. HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis. BMC Genomics 2011; 12: 549.
109. Baldassarre G, Belletti B, Battista S, et al. HMGA1 protein expression sensitizes cells to cisplatin-induced cell death. Oncogene 2005; 24: 6809-19.
110. Baldassarre G, Battista S, Belletti B, et al. Negative regulation of brca1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma. Mol Cell Biol 2003; 23: 2225-38.
111. Maloney SC, Adair JE, Smerdon MJ, Reeves R. Genespecific nucleotide excision repair is impaired in human cells expressing elevated levels of high mobility group A1 nonhistone proteins. DNA Repair (Amst). 2007; 6: 1371-9.
112. Adair JE, Maloney SC, Dement GA, Wertzler KJ, Smerdon MJ, Reeves R. High-mobility group A1 proteins inhibit expression of nucleotide excision repair factor xeroderma pigmentosum group A. Cancer Res 2007; 67: 6044-52.
113. Satou W, Suzuki T, Noguchi T, Ogino H, Fujii M, Ayusawa D. AT-hook proteins stimulate induction of senescence markers triggered by 5-bromodeoxyuridine in mammalian cells. Exp Gerontol 2004; 39: 173-9.
114. Narita M, Narita M, Krizhanovsky V, et al. A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation. Cell 2006; 126: 503-14.
115. Markowski DN, Bartnitzke S, Belge G, Drieschner N, Helmke BM, Bullerdiek J. Cell culture and senescence in uterine fibroids. Cancer Genet Cytogenet 2010; 202: 53-7.
116. Farnet CM, Bushman FD. HIV-1 cDNA integration: Requirement of HMG I(Y) protein for function of preintegration complexes in vitro. Cell 1997; 88: 483-92.
117. Shah SN, Cope L, Poh W, et al. Hmga1: A master regulator of tumor progression in triple-negative breast cancer cells. PLoS One 2013; 8: e63419.
118. Di Cello F, Dhara S, Hristov AC, et al. Inactivation of the Cdkn2a locus cooperates with HMGA1 to drive T-cell leukemogenesis. Leuk Lymphoma 2013; 54: 1762-8.
119. Roy S, Di Cello F, Kowalski J, et al. Hmga1 overexpression correlates with relapse in childhood B-lineage acute lymphoblastic leukemia. Leuk Lymphoma 2013; 54: 2565-7.
120. Munoz J, Stange DE, Schepers AG, et al. The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent '+4' cell markers. EMBO J 2012; 31: 3079-91
121. Saitoh Y, Laemmli UK. Metaphase chromosome structure: Bands arise from a differential folding path of the highly ATrich scaffold. Cell 1994; 76: 609-22.
122. Girard F, Bello B, Laemmli UK, Gehring WJ. In vivo analysis of scaffold-associated regions in drosophila: A synthetic highaffinity SAR binding protein suppresses position effect variegation. EMBO J 1998; 17: 2079-85.
123. Zhao K, Kas E, Gonzalez E, Laemmli UK. SAR-dependent mobilization of histone H1 by HMG-I/Y in vitro: Hmg-I/Y is enriched in H1-depleted chromatin. EMBO J 1993; 12: 3237-47.
124. Strick R, Laemmli UK. SARS are cis DNA elements of chromosome dynamics: Synthesis of a SAR repressor protein. Cell 1995; 83: 1137-48.
125. Mirkovitch J, Mirault ME, Laemmli UK. Organization of the higher-order chromatin loop: Specific DNA attachment sites on nuclear scaffold. Cell 1984; 39: 223-32.
126. Falvo JV, Thanos D, Maniatis T. Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y). Cell 1995; 83: 1101-11.
127. Thanos D, Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 1995; 83: 1091-100.
128. Du W, Maniatis T. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Proc Natl Acad Sci U S A 1994; 91: 11318-22.
129. Thanos D, Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa b-dependent virus induction of the human IFN-beta gene. Cell 1992; 71: 777-89.
130. Munshi N, Agalioti T, Lomvardas S, Merika M, Chen G, Thanos D. Coordination of a transcriptional switch by HMGI(Y) acetylation. Science 2001; 293: 1133-6.
131. Parekh BS, Maniatis T. Virus infection leads to localized hyperacetylation of histones H3 and H4 at the IFN-beta promoter. Mol Cell 1999; 3: 125-9.
132. Panne D, Maniatis T, Harrison SC. Crystal structure of ATF- 2/c-jun and IRF-3 bound to the interferon-beta enhancer. Embo J 2004; 23: 4384-93.
133. Kim TK, Maniatis T. The mechanism of transcriptional synergy of an in vitro assembled interferon-beta enhanceosome. Mol Cell 1997; 1: 119-29.
134. Munshi N, Merika M, Yie J, Senger K, Chen G, Thanos D. Acetylation of HMG I(Y) by CBP turns off IFN beta expression by disrupting the enhanceosome. Mol Cell 1998; 2: 457-67.
135. Merika M, Williams AJ, Chen G, Collins T, Thanos D. Recruitment of CBP/p300 by the IFN beta enhanceosome is required for synergistic activation of transcription. Mol Cell 1998; 1: 277-87.
136. Yie J, Merika M, Munshi N, Chen G, Thanos D. The role of HMG I(Y) in the assembly and function of the IFN-beta enhanceosome. Embo J 1999; 18: 3074-89.
137. Dragan AI, Carrillo R, Gerasimova TI, Privalov PL. Assembling the human IFN-beta enhanceosome in solution. J Mol Biol 2008; 384: 335-48.
138. Panne D, Maniatis T, Harrison SC. An atomic model of the interferon-beta enhanceosome. Cell 2007; 129: 1111-23.
139. Apostolou E, Thanos D. Virus infection induces NF-kappabdependent interchromosomal associations mediating monoallelic IFN-beta gene expression. Cell 2008; 134: 85-96.
140. Ford E, Thanos D. The transcriptional code of human IFNbeta gene expression. Biochim Biophys Acta 2010; 1799: 328-36.
141. Krech AB, Wulff D, Grasser KD, Feix G. Plant chromosomal HMGI/Y proteins and histone H1 exhibit a protein domain of common origin. Gene 1999; 230: 1-5.
142. Dhar A, Hu J, Reeves R, Resar LM, Colburn NH. Dominantnegative c-jun (tam67) target genes: HMGA1 is required for tumor promoter-induced transformation. Oncogene 2004; 23: 4466-76.
143. Scala S, Portella G, Fedele M, Chiappetta G, Fusco A. Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias. Proc Natl Acad Sci U S A 2000; 97: 4256-61.
144. Battista S, Pentimalli F, Baldassarre G, et al. Loss of HMGA1 gene function affects embryonic stem cell lymphohematopoietic differentiation. FASEB J 2003; 17: 1496-8.
145. Fedele M, Fidanza V, Battista S, et al. Haploinsufficiency of the HMGA1 gene causes cardiac hypertrophy and myelolymphoproliferative disorders in mice. Cancer Res 2006; 66: 2536-43.
146. Visone R, Iuliano R, Palmieri D, et al. HMGA1 null mice are less susceptible to chemically induced skin carcinogenesis. Eur J Cancer 2008; 44: 318-25.
147. Oshima M, Oshima H, Kitagawa K, Kobayashi M, Itakura C, Taketo M. Loss of Apc heteroxygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. Proc Natl Acad Sci U S A 1995; 92: 4481-6.
148. Warburg O. On the origin of cancer cells. Science 1956; 123: 309-14.
149. Warburg O. On respiratory impairment in cancer cells. Science 1956; 124: 269-70.
150. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011; 144: 646-74.
151. Williams MD, Reeves R, Resar LMS, Hill HH, Jr. Metabolomics of colorectal cancer (CRC): past and current analytical platforms. Analytical Bioanalytical Chem 2013; 405: 5013-30.
152. Williams MD, Zhang X, Belton AS, et al. HMGA1 drives metabolomics reprogramming of intenstinal epithelium during hyperproliferation, polyposis and colorectal carcinogenesis. J Proteome Res 2015; 14: 1420-31.
153. Williams MD, Zhang X, Park J-J, Siems WF, et al. Characterizing metabolic changes in human colorectal cancer. Anal Bioanal Chem 2015; 407: 4581-95.
154. Dang CV, Le A, Gao P. Myc-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009; 15: 6479-83.
155. Jones RG, Thompson CB. Tumor suppressors and cell metabolism: A recipe for cancer growth. Genes Dev 2009; 23: 537-48.
156. Dang CV HM, Sun P, Le A, Gao P. Therapeutic targeting of cancer cell metabolism. J Mol Med (Berl) 2001; 89: 205-12.
157. Dang CV. Links between metabolism and cancer. Genes Dev 2012; 26: 877-90.
158. Le A, Cooper CR, Gouw AM, et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci U S A 2010; 107: 2037-42.
159. Alzheimer's Association. 2010 Alzheimer's disease facts and figures. Alzheimers Dement 2010; 6: 158-94.
160. White AR, Du T, Laughton KM, et al. Degradation of the alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity. J Biol Chem 2006; 281: 17670-80.
161. Chiang PK, Lam MA, Luo Y. The many faces of amyloid beta in alzheimer's disease. Curr Mol Med 2008; 8: 580-4.
162. Selkoe DJ, Wolfe MS. Presenilin: Running with scissors in the membrane. Cell 2007; 131: 215-21.
163. Sgarra R, Tessari MA, Di Bernardo J, et al. Discovering high mobility group a molecular partners in tumour cells. Proteomics 2005; 5: 1494-506.
164. Young NL, Plazas-Mayorca MD, DiMaggio PA, et al. Collective mass spectrometry approaches reveal broad and combinatorial modification of high mobility group protein a1a. J Am Soc Mass Spectrom 2010; 21: 960-70.
165. Coelho LF, Magno de Freitas Almeida G, Mennechet FJ, Blangy A, Uze G. Interferon-alpha and beta differentially regulate osteoclastogenesis: Role of differential induction of chemokine CXCL11 expression. Proc Natl Acad Sci U S A 2005; 102: 11917-22.
166. Chau KY, Keane-Myers AM, Fedele M, et al. IFN-gamma gene expression is controlled by the architectural transcription factor HMGA1. Int Immunol 2005; 17: 297-306.
167. Himes SR, Reeves R, Attema J, Nissen M, Li Y, Shannon MF. The role of high-mobility group I(Y) proteins in expression of IL-2 and T cell proliferation. J Immunol 2000; 164: 3157-68.
168. Shannon MF, Himes SR, Attema J. A role for the architectural transcription factors HMGI(Y) in cytokine gene transcription in T cells. Immunol Cell Biol 1998; 76: 461-6.
169. Chuvpilo S, Schomberg C, Gerwig R, et al. Multiple closelylinked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter. Nucleic Acids Res 1993; 21: 5694-704.
170. Trentin L, Zambello R, Agostini C, et al. Expression and regulation of tumor necrosis factor, interleukin-2, and hematopoietic growth factor receptors in B-cell chronic lymphocytic leukemia. Blood 1994; 84: 4249-56.
171. Kay NE, Pittner BT. Il-4 biology: Impact on normal and leukemic CLL B cells. Leuk Lymphoma 2003; 44: 897-903.
172. Ma A, Koka R, Burkett P. Diverse functions of Il-2, IL-15, and Il-7 in lymphoid homeostasis. Annu Rev Immunol 2006; 24: 657-79.
173. Whitley MZ, Thanos D, Read MA, Maniatis T, Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol 1994; 14: 6464-75.
174. Olofsson AM, Arfors KE, Ramezani L, Wolitzky BA, Butcher EC, von Andrian UH. E-selectin mediates leukocyte rolling in interleukin-1-treated rabbit mesentery venules. Blood 1994; 84: 2749-58.
175. Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database (Oxford) 2010; 2010: baq020.
176. Baron RM, Lopez-Guzman S, Riascos DF, et al. Distamycin A inhibits HMGA1-binding to the P-selectin promoter and attenuates lung and liver inflammation during murine endotoxemia. PLoS One 2010; 5: e10656.
177. John S, Reeves RB, Lin JX, et al. Regulation of cell-typespecific interleukin-2 receptor alpha-chain gene expression: Potential role of physical interactions between ELF-1, HMGI(Y), and NF-kappa B family proteins. Mol Cell Biol 1995; 15: 1786-96.
178. John S, Robbins CM, Leonard WJ. An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds STAT5, ELF-1, HMG-I(Y) and a gata family protein. EMBO J 1996; 15: 5627-35.
179. Reeves R, Leonard WJ, Nissen MS. Binding of HMG-I(Y) imparts architectural specificity to a positioned nucleosome on the promoter of the human interleukin-2 receptor alpha gene. Mol Cell Biol 2000; 20: 4666-79.
180. Milani P, Marilley M, Sanchez-Sevilla A, et al. Mechanics of the IL2ra gene activation revealed by modeling and atomic force microscopy. PLoS One 2011; 6: e18811.
181. Fashena SJ, Reeves R, Ruddle NH. A poly(da-dt) upstream activating sequence binds high-mobility group I protein and contributes to lymphotoxin (tumor necrosis factor-beta) gene regulation. Mol Cell Biol 1992; 12: 894-903.
182. Welniak LA, Kuprash DV, Tumanov AV, et al. Peyer patches are not required for acute graft-versus-host disease after myeloablative conditioning and murine allogeneic bone marrow transplantation. Blood 2006; 107: 410-2.
183. Drutskaya MS, Efimov GA, Kruglov AA, Kuprash DV, Nedospasov SA. Tumor necrosis factor, lymphotoxin and cancer. IUBMB Life 2010; 62: 283-9.
184. Wood LD, Farmer AA, Richmond A. HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene. Nucleic Acids Res 1995; 23: 4210-9.
185. Chen J, Petrus M, Bamford R, et al. Increased serum soluble IL-15R alpha levels in T-cell large granular lymphocyte leukemia. Blood 2012; 119: 137-43.
186. Steel JC, Waldmann TA, Morris JC. Interleukin-15 biology and its therapeutic implications in cancer. Trends Pharmacol Sci 2012; 33: 35-41.
187. Lin SC. Identification of an NF-Y/HMG-I(Y)-binding site in the human IL-10 promoter. Mol Immunol 2006; 43: 1325-31.
188. Kang YJ, Yang SJ, Park G, et al. A novel function of interleukin-10 promoting self-renewal of hematopoietic stem cells. Stem Cells 2007; 25: 1814-22.
189. Himes SR, Coles LS, Reeves R, Shannon MF. High mobility group protein I(Y) is required for function and for c-rel binding to CD28 response elements within the GC-CSF and IL-2 promoters. Immunity 1996; 5: 479-89.
190. Schweizerhof M, Stosser S, Kurejova M, et al. Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nat Med 2009; 15: 802-7.
191. Bagga R, Emerson BM. An hmg i/y-containing repressor complex and supercoiled DNA topology are critical for longrange enhancer-dependent transcription in vitro. Genes Dev 1997; 11: 629-39.
192. Kim J, Reeves R, Rothman P, Boothby M. The non-histone chromosomal protein HMG-I(Y) contributes to repression of the immunoglobulin heavy chain germ-line epsilon RNA promoter. Eur J Immunol 1995; 25: 798-808.
193. Lewis RT, Andreucci A, Nikolajczyk BS. PU.1-mediated transcription is enhanced by HMG-I(Y)-dependent structural mechanisms. J Biol Chem 2001; 276: 9550-7.
194. Andreucci A, Reeves R, McCarthy KM, Nikolajczyk BS. Dominant-negative hmga1 blocks mu enhancer activation through a novel mechanism. Biochem Biophys Res Commun 2002; 292: 427-33.
195. McCarthy KM, McDevit D, Andreucci A, Reeves R, Nikolajczyk BS. HMGA1 co-activates transcription in B cells through indirect association with DNA. J Biol Chem 2003; 278: 42106-14.
196. Skalnik DG, Neufeld EJ. Sequence-specific binding of HMGI(Y) to the proximal promoter of the gp91-phox gene. Biochem Biophys Res Commun 1992; 187: 563-9.
197. Efremov DG, Laurenti L. The syk kinase as a therapeutic target in leukemia and lymphoma. Expert Opin Investig Drugs 2011; 20: 623-36.
198. Martinez Hoyos J, Fedele M, Battista S, et al. Identification of the genes up- and down-regulated by the high mobility group A1 (HMGA1) proteins: Tissue specificity of the HMGA1- dependent gene regulation. Cancer Res 2004; 64: 5728-35.
199. Molkentin JD. The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem 2000; 275: 38949-52.
200. Kodo K, Nishizawa T, Furutani M, et al. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling. Proc Natl Acad Sci U S A 2009; 106: 13933-8.
201. Wani MA, Means RT Jr, Lingrel JB. Loss of LKLF function results in embryonic lethality in mice. Transgenic Res 1998; 7: 229-38.
202. Saavedra MT, Patterson AD, West J, et al. Abrogation of anti-inflammatory transcription factor LKLF in neutrophildominated airways. Am J Respir Cell Mol Biol 2008; 38: 679-88.
203. Gitenay D, Baron VT. Is EGR1 a potential target for prostate cancer therapy? Future Oncol 2009; 5: 993-1003.
204. Chin MT, Pellacani A, Wang H, et al. Enhancement of serumresponse factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y). J Biol Chem 1998; 273: 9755-60.
205. Dang CV, Resar LM, Emison E, et al. Function of the c-myc oncogenic transcription factor. Exp Cell Res 1999; 253: 63-77.
206. Hillion J, Belton AM, Shah SN, et al. Nanoparticle delivery of inhibitory signal transducer and activator of transcription 3 (STAT3) G-quartet oligonucleotides blocks tumor growth in HMGA1 transgenic model of T-cell leukemia. Leuk Lymphoma 2014; 55: 1194-7.
207. Turkson J, Zhang S, Palmer J, et al. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity. Mol Cancer Ther 2004; 3: 1533-42.
208. Yu H, Pardoll D, Jove R. Stats in cancer inflammation and immunity: A leading role for STAT3. Nat Rev Cancer 2009; 9: 798-809.
209. Yue P, Turkson J. Targeting STAT3 in cancer: How successful are we? Expert Opin Investig Drugs 2009; 18: 45-56.
210. Katoh M, Katoh M. Human FOX gene family (review). Int J Oncol 2004; 25: 1495-500.
211. Kimura N, Nakashima K, Ueno M, Kiyama H, Taga T. A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain. Brain Res Dev Brain Res 1999; 115: 183-93.
212. Yang Y, Xu J, Niu Y, Bromberg JS, Ding Y. T-bet and eomesodermin play critical roles in directing T cell differentiation to Th1 versus Th17. J Immunol 2008; 181: 8700-10.
213. Narayanan S, Silva R, Peruzzi G, et al. Human Th1 cells that express CD300a are polyfunctional and after stimulation upregulate the T-box transcription factor eomesodermin. PLoS One 2010; 5: e10636.
214. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704-15.
215. Martinez-Hoyos J, Ferraro A, Sacchetti S, et al. HAND1 gene expression is negatively regulated by the high mobility group A1 proteins and is drastically reduced in human thyroid carcinomas. Oncogene 2009; 28: 876-85.
216. Chang MS, Uozaki H, Chong JM, et al. Cpg island methylation status in gastric carcinoma with and without infection of Epstein-Barr virus. Clin Cancer Res 2006; 12: 2995-3002.
217. Oue N, Mitani Y, Motoshita J, et al. Accumulation of DNA methylation is associated with tumor stage in gastric cancer. Cancer 2006; 106: 1250-9.
218. Maekita T, Nakazawa K, Mihara M, et al. High levels of aberrant DNA methylation in helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 2006; 12: 989-95.
219. Imura M, Yamashita S, Cai LY, et al. Methylation and expression analysis of 15 genes and three normally methylated genes in 13 ovarian cancer cell lines. Cancer Lett 2006; 241: 213-20.
220. Settembre C, Di Malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science 2011; 332: 1429-33.
221. Esposito F, Tornincasa M, Chieffi P, De Martino I, Pierantoni GM, Fusco A. High-mobility group A1 proteins regulate p53- mediated transcription of Bcl-2 gene. Cancer Res 2010; 70: 5379-88.
222. Treff NR, Pouchnik D, Dement GA, Britt RL, Reeves R. Highmobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells. Oncogene 2004; 23: 777-85.
223. Treff NR, Dement GA, Adair JE, et al. Human KIT ligand promoter is positively regulated by HMGA1 in breast and ovarian cancer cells. Oncogene 2004; 23: 8557-62.
224. Quest AF, Gutierrez-Pajares JL, Torres VA. Caveolin-1: An ambiguous partner in cell signalling and cancer. J Cell Mol Med 2008; 12: 1130-50.
225. Elsheikh SE, Green AR, Rakha EA, et al. Caveolin 1 and caveolin 2 are associated with breast cancer basal-like and triple-negative immunophenotype. Br J Cancer 2008; 99: 327-34.
226. Schwahn DJ, Medina D. p96, a MAPK-related protein, is consistently downregulated during mouse mammary carcinogenesis. Oncogene 1998; 17: 1173-8.
227. Albertsen HM, Smith SA, Melis R, et al. Sequence, genomic structure, and chromosomal assignment of human DOC-2. Genomics 1996; 33: 207-13.
228. Mok SC, Chan WY, Wong KK, et al. DOC-2, a candidate tumor suppressor gene in human epithelial ovarian cancer. Oncogene 1998; 16: 2381-7.
229. Zhang Y, Finegold MJ, Porteu F, Kanteti P, Wu MX. Development of T-cell lymphomas in Emu-IEX-1 mice. Oncogene 2003; 22: 6845-51.
230. Perrella MA, Pellacani A, Wiesel P, et al. High mobility group- I(Y) protein facilitates nuclear factor-kappab binding and transactivation of the inducible nitric-oxide synthase promoter/enhancer. J Biol Chem 1999; 274: 9045-52.
231. Takamiya R, Baron RM, Yet SF, Layne MD, Perrella MA. High mobility group A1 protein mediates human nitric oxide synthase 2 gene expression. FEBS Lett 2008; 582: 810-4.
232. Pellacani A, Wiesel P, Razavi S, et al. Down-regulation of high mobility group-I(Y) protein contributes to the inhibition of nitric-oxide synthase 2 by transforming growth factor-beta1. J Biol Chem 2001; 276: 1653-9.
233. Darville MI, Terryn S, Eizirik DL. An octamer motif is required for activation of the inducible nitric oxide synthase promoter in pancreatic beta-cells. Endocrinology 2004; 145: 1130-6.
234. Rao CV. Nitric oxide signaling in colon cancer chemoprevention. Mutat Res 2004; 555: 107-19.
235. Ye Y, Martinez JD, Perez-Polo RJ, Lin Y, Uretsky BF, Birnbaum Y. The role of eNOS, iNOS, and NF-kappaB in upregulation and activation of cyclooxygenase-2 and infarct size reduction by atorvastatin. Am J Physiol Heart Circ Physiol 2008; 295: H343-51.
236. Kim SF, Huri DA, Snyder SH. Inducible nitric oxide synthase binds, s-nitrosylates, and activates cyclooxygenase-2. Science 2005; 310: 1966-70.
237. Chin MT, Pellacani A, Wang H, et al. of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor hmg-I(Y). J Biol Chem 1998; 273: 9755-60.
238. Bell RD, Deane R, Chow N, et al. SRF and myocardin regulate LRP-mediated amyloid-beta clearance in brain vascular cells. Nat Cell Biol 2009; 11: 143-53.
239. Foster LC, Wiesel P, Huggins GS, et al. Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1beta in vascular smooth muscle cells. FASEB J 2000; 14: 368-78.
240. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003; 100: 3983-8.
241. Li F, Tiede B, Massague J, Kang Y. Beyond tumorigenesis: Cancer stem cells in metastasis. Cell Res 2007; 17: 3-14.
242. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 2006; 12: 1167-74.
243. Ruzinova MB, Benezra R. Id proteins in development, cell cycle and cancer. Trends Cell Biol 2003; 13: 410-8.
244. Melillo RM, Pierantoni GM, Scala S, et al. Critical role of the HMGI(Y) proteins in adipocytic cell growth and differentiation. Mol Cell Biol 2001; 21: 2485-95.
245. Nagel S, Scherr M, Kel A, et al. Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) t-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1. Cancer Res 2007; 67: 1461-71.
246. Yang YJ, Cao YJ, Bo SM, Peng S, Liu WM, Duan EK. Leptindirected embryo implantation: Leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells. Anim Reprod Sci 2006; 92: 155-67.
247. Zucker S, Cao J. Selective matrix metalloproteinase (MMP) inhibitors in cancer therapy: Ready for prime time? Cancer Biol Ther 2009; 8: 2371-3.
248. Palavalli LH, Prickett TD, Wunderlich JR, et al. Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma. Nat Genet 2009; 41: 518-20.
249. Thirumangalakudi L, Samany PG, Owoso A, Wiskar B, Grammas P. Angiogenic proteins are expressed by brain blood vessels in alzheimer's disease. J Alzheimers Dis 2006; 10: 111-8.
250. Lorenzl S, Albers DS, Relkin N, et al. Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. Neurochem Int 2003; 43: 191-6.
251. Reiser J, Adair B, Reinheckel T. Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 2010; 120: 3421-31.
252. Wang L, Chen S, Zhang M, et al. Legumain: A biomarker for diagnosis and prognosis of human ovarian cancer. J Cell Biochem 2012; 113: 2679-86.
253. Wolk K, Grutz G, Witte K, Volk HD, Sabat R. The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes. Genes Immun 2005; 6: 452-6.
254. Lee TK, Murthy SR, Cawley NX, et al. An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers. J Clin Invest 2011; 121: 880-92.
255. Ji YS, Xu Q, Schmedtje JF Jr. Hypoxia induces high-mobilitygroup protein I(Y) and transcription of the cyclooxygenase-2 gene in human vascular endothelium. Circ Res 1998; 83: 295-304.
256. Di Cello F, Hillion J, Kowalski J, et al. Cyclooxygenase inhibitors block uterine tumorigenesis in HMGA1a transgenic mice and human xenografts. Mol Cancer Ther 2008; 7: 2090-5.
257. Hillion J, Smail SS, Di Cello F, et al. The HMGA1-COX-2 axis: A molecular pathway leading to tumor progression in human pancreatic adenocarcinoma. Pancreatology 2012; 12: 372-9.
258. Sutcliffe S, Neace C, Magnuson NS, Reeves R, Alderete JF. Trichomonosis, a common curable STI, and prostate carcinogenesis--a proposed molecular mechanism. PLoS Pathog 2012; 8: e1002801.
259. Chau KY, Munshi N, Keane-Myers A, et al. The architectural transcription factor high mobility group I(Y) participates in photoreceptor-specific gene expression. J Neurosci 2000; 20: 7317-24.
260. Chen S, Wang QL, Nie Z, et al. Crx, a novel Otx-like pairedhomeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 1997; 19: 1017-30.
261. Duncan B, Zhao K. HMGA1 mediates the activation of the CRYAB promoter by BRG1. DNA Cell Biol 2007; 26: 745-52.
262. Brunetti A, Manfioletti G, Chiefari E, Goldfine ID, Foti D. Transcriptional regulation of human insulin receptor gene by the high-mobility group protein HMGI(Y). FASEB J 2001; 15: 492-500.
263. Foti D, Iuliano R, Chiefari E, Brunetti A. A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription. Mol Cell Biol 2003; 23: 2720-32.
264. Chiefari E, Tanyolac S, Paonessa F, et al. Functional variants of the HMGA1 gene and type 2 diabetes mellitus. JAMA 2011; 305: 903-12.
265. Arnaldez FI, Helman LJ. Targeting the insulin growth factor receptor 1. Hematol Oncol Clin North Am 2012; 26: 527-42, vii-viii.
266. Allander SV, Durham SK, Scheimann AO, Wasserman RM, Suwanichkul A, Powell DR. Hepatic nuclear factor 3 and high mobility group I/Y proteins bind the insulin response element of the insulin-like growth factor-binding protein-1 promoter. Endocrinology 1997; 138: 4291-300.
267. Iiritano S, Chiefari E, Ventura V, et al. The HMGA1-IGFI/ IGFBP system: A novel pathway for modulating glucose uptake. Mol Endocrinol 2012; 26: 1578-89.
268. Georges RB, Adwan H, Hamdi H, Hielscher T, Linnemann U, Berger MR. The insulin-like growth factor binding proteins 3 and 7 are associated with colorectal cancer and liver metastasis. Cancer Biol Ther 2011; 12: 69-79.
269. Ha TK, Her NG, Lee MG, et al. Caveolin-1 increases aerobic glycolysis in colorectal cancers by stimulating HMGA1- mediated GLUT3 transcription. Cancer Res 2012; 72: 4097-109.
270. Tharmalingam S, Daulat AM, Antflick JE, et al. Calciumsensing receptor modulates cell adhesion and migration via integrins. J Biol Chem 2011; 286: 40922-33.
271. Gridley T. Notch signaling and inherited disease syndromes. Hum Mol Genet 2003; 12 Spec No 1: R9-13.
272. Chillakuri CR, Sheppard D, Lea SM, Handford PA. Notch receptor-ligand binding and activation: Insights from molecular studies. Semin Cell Dev Biol 2012; 23: 421-8.
273. Ferrando AA. The role of NOTCH1 signaling in T-ALL. Hematology Am Soc Hematol Educ Program 2009: 353-61.
274. Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A. Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 2006; 174: 175-83.
275. Glinsky GV. Death-from-cancer signatures and stem cell contribution to metastatic cancer. Cell Cycle 2005; 4: 1171-5.
276. Glinsky GV. Genomic models of metastatic cancer: Functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated polycomb group (PcG) protein chromatin silencing pathway. Cell Cycle 2006; 5: 1208-16.
277. Pierantoni GM, Conte A, Rinaldo C, et al. Deregulation of HMGA1 expression induces chromosome instability through regulation of spindle assembly checkpoint genes. Oncotarget 2015; 6: 17342-53.
278. Kirkland SC. Type 1 collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells. Br J Cancer 2009; 101: 320-6.
279. Haque I, Mehta S, Majumder M, et al. Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis. Mol Cancer 2011; 10: 8.
280. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834-8.
281. Yanagisawa BL, Resar LM. Hitting the bull’s eye: Targeting HMGA1 in cancer stem cells. Expert Rev Anticancer Ther 2014; 14: 23-30.
282. Huso TH, Resar LM. The high mobility group A1 molecular switch: turning on cancer - can we turn it off? Expert Opin Ther Targets 2014; 18: 541-53.
283. Pedulla ML, Treff NR, Resar LM, Reeves R. Sequence and analysis of the murine HMGIY (HMGA1) gene locus. Gene 2001; 271: 51-8
284. Hommura F, Katabami M, Leaner VD, et al. HMG-I/Y is a cjun/ activator protein-1 target gene and is necessary for c-juninduced anchorage-independent growth in rat1a cells. Mol Cancer Res 2004; 2: 305-14.
285. Bush BM, Brock AT, Deng JA, Nelson RA, Sumter TF. The Wnt/beta-catenin/T-cell factor 4 pathway up-regulates highmobility group A1 expression in colon cancer. Cell Biochem Funct 2013; 31: 228-36.
286. Lund T, Holtlund J, Laland SG. On the phosphorylation of low molecular mass HMG (high mobility group) proteins in Ehrlich ascites cells. FEBS Lett 1985; 180: 275-9.
287. Elton TS, Reeves R. Purification and postsynthetic modifications of friend erythroleukemic cell high mobility group protein HMG-I. Anal Biochem 1986; 157: 53-62.
288. Reeves R, Langan TA, Nissen MS. Phosphorylation of the DNA-binding domain of nonhistone high-mobility group I protein by cdc2 kinase: Reduction of binding affinity. Proc Natl Acad Sci U S A 1991; 88: 1671-5.
289. Nissen MS, Langan TA, Reeves R. Phosphorylation by cdc2 kinase modulates DNA binding activity of high mobility group I nonhistone chromatin protein. J Biol Chem 1991; 266: 19945-52.
290. Piekielko A, Drung A, Rogalla P, et al. Distinct organization of DNA complexes of various HMGI/Y family proteins and their modulation upon mitotic phosphorylation. J Biol Chem 2001; 276: 1984-92.
291. Zhang Q, Wang Y. Homeodomain-interacting protein kinase- 2 (HIPK2) phosphorylates HMGA1a at ser-35, thr-52, and thr-77 and modulates its DNA binding affinity. J Proteome Res 2007; 6: 4711-9.
292. Sgarra R, Diana F, Bellarosa C, et al. During apoptosis of tumor cells HMGA1a protein undergoes methylation: Identification of the modification site by mass spectrometry. Biochemistry 2003; 42: 3575-85.
293. Maurizio E, Cravello L, Brady L, et al. Conformational role for the C-terminal tail of the intrinsically disordered high mobility group A (HMGA) chromatin factors. J Proteome Res 2011; 10: 3283-91.
294. Sgarra R, Lee J, Tessari MA, et al. The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6. J Biol Chem 2006; 281: 3764-72.
295. Tran JC, Zamdborg L, Ahlf DR, et al. Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature 2011; 480: 254-8.
296. Belton A, Xian L, Huso T, et al. STAT3 inhibitor has potent anti-tumor activity in B-lineage acute lymphoblastic leukemia cells overexpressing the High Mobility Group A1 (HMGA1)- STAT3 pathway. Leuk Lymphoma 2016: 1-4. [Epub ahead of print].
297. Cartharius K, Frech K, Grote K, et al. MatInspector and beyong: promoter analysis based on transcription factor binding sites. Bioinformatics 2005; 21: 2933-42.