Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 40, 2011, Pages

  Wang, Lixin ^a   Brugge, Joan S ^b   Janes, Kevin A ^a  

^a University of Virginia   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Heterogeneity; Stochastic; Systems biology; Triple negative

Indexed keywords

ATROGIN 1; CALCYCLIN; CAVEOLIN 1; CYCLIN B1; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLIN DEPENDENT KINASE INHIBITOR 1C; CYCLIN I; CYTOKERATIN 10; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; MANGANESE SUPEROXIDE DISMUTASE; MEMBRANE PROTEIN; MESSENGER RNA; PEROXIREDOXIN 6; PROTEIN BCL2L13; PROTEIN BTG1; PROTEIN SEMA3C; PROTEIN SESN1; TRANSCRIPTION FACTOR FOXO; TRANSCRIPTION FACTOR RUNX1; TRANSCRIPTION FACTOR SOX4; UBIQUITIN; UNCLASSIFIED DRUG;

ACINAR CELL; ARTICLE; BREAST EPITHELIUM; CELL CYCLE ARREST; CELL PROLIFERATION; CELL STRUCTURE; DOWN REGULATION; EPITHELIUM CELL; GENE AMPLIFICATION; GENE EXPRESSION; GENE EXPRESSION PROFILING; MORPHOGENESIS; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; TUMOR GROWTH; UPREGULATION;

ACINAR CELLS; BREAST NEOPLASMS; CELL LINE, TUMOR; CHROMATIN IMMUNOPRECIPITATION; COMPUTATIONAL BIOLOGY; CORE BINDING FACTOR ALPHA 2 SUBUNIT; FEMALE; FLUORESCENT ANTIBODY TECHNIQUE; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HUMANS; IMMUNOBLOTTING; IN SITU HYBRIDIZATION, FLUORESCENCE; LENTIVIRUS; MORPHOGENESIS; RNA INTERFERENCE; SYSTEMS BIOLOGY;

EID: 80053645783     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1103423108     Document Type: Article

References (91)

1. Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836-840. (Pubitemid 34845918)
2. Janes KA, Wang CC, Holmberg KJ, Cabral K, Brugge JS (2010) Identifying single-cell molecular programs by stochastic profiling. Nat Methods 7:311-317.
3. Singh DK, et al. (2010) Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities. Mol Syst Biol 6:369.
4. Fidler IJ, Kripke ML (1977) Metastasis results from preexisting variant cells within a malignant tumor. Science 197:893-895. (Pubitemid 8168759)
5. Southam CM, Brunschwig A (1961) Quantitative studies of autotransplantation of human cancer. Cancer 14:971-978.
6. Loo LH, et al. (2009) Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes. J Cell Biol 187:375-384.
7. Sharma SV, et al. (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141:69-80.
8. Spencer SL, Gaudet S, Albeck JG, Burke JM, Sorger PK (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 459:428-432.
9. Brock A, Chang H, Huang S (2009) Non-genetic heterogeneity - a mutationindependent driving force for the somatic evolution of tumours. Nat Rev Genet 10: 336-342.
10. Niepel M, Spencer SL, Sorger PK (2009) Non-genetic cell-to-cell variability and the consequences for pharmacology. Curr Opin Chem Biol 13:556-561.
11. Altschuler SJ, Wu LF (2010) Cellular heterogeneity: Do differences make a difference? Cell 141:559-563.
12. Golding I, Paulsson J, Zawilski SM, Cox EC (2005) Real-time kinetics of gene activity in individual bacteria. Cell 123:1025-1036. (Pubitemid 41785418)
13. Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S (2006) Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4:e309.
14. Yu J, Xiao J, Ren X, Lao K, Xie XS (2006) Probing gene expression in live cells, one protein molecule at a time. Science 311:1600-1603.
15. Komili S, Silver PA (2008) Coupling and coordination in gene expression processes: A systems biology view. Nat Rev Genet 9:38-48. (Pubitemid 350277299)
16. Zenklusen D, Larson DR, Singer RH (2008) Single-RNA counting reveals alternative modes of gene expression in yeast. Nat Struct Mol Biol 15:1263-1271.
17. Chubb JR, Trcek T, Shenoy SM, Singer RH (2006) Transcriptional pulsing of a developmental gene. Curr Biol 16:1018-1025. (Pubitemid 43728209)
18. Elf J, Li GW, Xie XS (2007) Probing transcription factor dynamics at the singlemolecule level in a living cell. Science 316:1191-1194. (Pubitemid 46877481)
19. Janicki SM, et al. (2004) From silencing to gene expression: Real-time analysis in single cells. Cell 116:683-698. (Pubitemid 38326727)
20. Gandhi SJ, Zenklusen D, Lionnet T, Singer RH (2011) Transcription of functionally related constitutive genes is not coordinated. Nat Struct Mol Biol 18:27-34.
21. Raj A, Rifkin SA, Andersen E, van Oudenaarden A (2010) Variability in gene expression underlies incomplete penetrance. Nature 463:913-918.
22. Iscove NN, et al. (2002) Representation is faithfully preserved in global cDNA amplified exponentially from sub-picogram quantities of mRNA. Nat Biotechnol 20: 940-943. (Pubitemid 35001134)
23. Emmert-Buck MR, et al. (1996) Laser capture microdissection. Science 274:998-1001. (Pubitemid 26398425)
24. Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410-7425. (Pubitemid 41637981)
25. Pierrou S, Hellqvist M, Samuelsson L, Enerbäck S, Carlsson P (1994) Cloning and characterization of seven human forkhead proteins: Binding site specificity and DNA bending. EMBO J 13:5002-5012. (Pubitemid 24319383)
26. Xuan Z, Zhang MQ (2005) From worm to human: Bioinformatics approaches to identify FOXO target genes. Mech Ageing Dev 126:209-215. (Pubitemid 40021803)
27. Kwon ES, Narasimhan SD, Yen K, Tissenbaum HA (2010) A new DAF-16 isoform regulates longevity. Nature 466:498-502.
28. Zhao Y, et al. (2010) Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat Cell Biol 12:665-675.
29. Hosaka T, et al. (2004) Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA 101: 2975-2980. (Pubitemid 38327721)
30. van der Horst A, et al. (2006) FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol 8:1064-1073.
31. Huang H, et al. (2005) Skp2 inhibits FOXO1 in tumor suppression through ubiquitinmediated degradation. Proc Natl Acad Sci USA 102:1649-1654.
32. Plas DR, Thompson CB (2003) Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J Biol Chem 278:12361-12366. (Pubitemid 36800220)
33. Essers MA, et al. (2004) FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK. EMBO J 23:4802-4812. (Pubitemid 40069710)
34. Brunet A, et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857-868. (Pubitemid 29165088)
35. Ramaswamy S, Nakamura N, Sansal I, Bergeron L, Sellers WR (2002) A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2:81-91. (Pubitemid 41043990)
36. van der Vos KE, Coffer PJ (2008) FOXO-binding partners: It takes two to tango. Oncogene 27:2289-2299.
37. Debnath J, Muthuswamy SK, Brugge JS (2003) Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30:256-268. (Pubitemid 36677560)
38. Ho KK, Myatt SS, Lam EW (2008) Many forks in the path: Cycling with FoxO. Oncogene 27:2300-2311. (Pubitemid 351501781)
39. Gross DN, van den Heuvel AP, Birnbaum MJ (2008) The role of FoxO in the regulation of metabolism. Oncogene 27:2320-2336. (Pubitemid 351501783)
40. Shi L, et al. (2006) The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotechnol 24: 1151-1161. (Pubitemid 44359727)
41. Newman JR, et al. (2006) Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441:840-846.
42. Kops GJ, et al. (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316-321.
43. Tothova Z, et al. (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128:325-339. (Pubitemid 46137992)
44. Das KC, Lewis-Molock Y, White CW (1995) Thiol modulation of TNF alpha and IL-1 induced MnSOD gene expression and activation of NF-kappa B. Mol Cell Biochem 148: 45-57.
45. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu Rev Immunol 18:621-663. (Pubitemid 30365393)
46. Janes KA, Yaffe MB (2006) Data-driven modelling of signal-transduction networks. Nat Rev Mol Cell Biol 7:820-828. (Pubitemid 44627475)
47. Bengtsson M, Ståhlberg A, Rorsman P, Kubista M (2005) Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels. Genome Res 15:1388-1392. (Pubitemid 41400905)
48. Warren L, Bryder D, Weissman IL, Quake SR (2006) Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR. Proc Natl Acad Sci USA 103: 17807-17812. (Pubitemid 44852241)
49. Keshava Prasad TS, et al. (2009) Human Protein Reference Database - 2009 update. Nucleic Acids Res 37:D767-D772.
50. Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2:28-36.
51. Lau QC, et al. (2006) RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res 66: 6512-6520. (Pubitemid 44085605)
52. Pratap J, et al. (2006) Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev 25:589-600. (Pubitemid 46071865)
53. Pratap J, et al. (2009) Ectopic runx2 expression in mammary epithelial cells disrupts formation of normal acini structure: Implications for breast cancer progression. Cancer Res 69:6807-6814.
54. Shore P (2005) A role for Runx2 in normal mammary gland and breast cancer bone metastasis. J Cell Biochem 96:484-489.
55. Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR (1996) AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321-330. (Pubitemid 26042836)
56. Silva FP, et al. (2003) Identification of RUNX1/AML1 as a classical tumor suppressor gene. Oncogene 22:538-547. (Pubitemid 36188611)
57. Miyoshi H, et al. (1991) t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 88:10431-10434. (Pubitemid 21915849)
58. Kadota M, et al. (2010) Delineating genetic alterations for tumor progression in the MCF10A series of breast cancer cell lines. PLoS One 5:e9201.
59. Yamamura Y, Lee WL, Inoue K, Ida H, Ito Y (2006) RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J Biol Chem 281:5267-5276. (Pubitemid 43847791)
60. Wildey GM, Howe PH (2009) Runx1 is a co-activator with FOXO3 to mediate transforming growth factor beta (TGFbeta)-induced Bim transcription in hepatic cells. J Biol Chem 284:20227-20239.
61. Zhang Y, Biggs JR, Kraft AS (2004) Phorbol ester treatment of K562 cells regulates the transcriptional activity of AML1c through phosphorylation. J Biol Chem 279: 53116-53125. (Pubitemid 40051813)
62. Tanaka T, et al. (1996) The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability. Mol Cell Biol 16:3967-3979. (Pubitemid 26199916)
63. Biggs JR, Peterson LF, Zhang Y, Kraft AS, Zhang DE (2006) AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation of AML1/RUNX1 by the anaphase-promoting complex. Mol Cell Biol 26:7420-7429. (Pubitemid 44547694)
64. Nakae J, Kitamura T, Silver DL, Accili D (2001) The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108:1359-1367. (Pubitemid 33107764)
65. Schafer ZT, et al. (2009) Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461:109-113.
66. Russo T, et al. (1995) A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress. J Biol Chem 270:29386-29391.
67. Clopton DA, Saltman P (1995) Low-level oxidative stress causes cell-cycle specific arrest in cultured cells. Biochem Biophys Res Commun 210:189-196.
68. Wiese AG, Pacifici RE, Davies KJ (1995) Transient adaptation of oxidative stress in mammalian cells. Arch Biochem Biophys 318:231-240.
69. Paik JH, et al. (2007) FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128:309-323.
70. Neve RM, et al. (2006) A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 10:515-527. (Pubitemid 44854747)
71. Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: A critical review. J Clin Oncol 26:2568-2581.
72. Essaghir A, Dif N, Marbehant CY, Coffer PJ, Demoulin JB (2009) The transcription of FOXO genes is stimulated by FOXO3 and repressed by growth factors. J Biol Chem 284:10334-10342.
73. Al-Mubarak B, Soriano FX, Hardingham GE (2009) Synaptic NMDAR activity suppresses FOXO1 expression via a cis-acting FOXO binding site: FOXO1 is a FOXO target gene. Channels (Austin) 3:233-238.
74. Fox MD, et al. (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA 102:9673-9678. (Pubitemid 40981739)
75. Blyth K, et al. (2006) Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res 66:2195-2201.
76. Hu K, Ji L, Applegate KT, Danuser G, Waterman-Storer CM (2007) Differential transmission of actin motion within focal adhesions. Science 315:111-115. (Pubitemid 46196992)
77. Wheeler JC, Shigesada K, Gergen JP, Ito Y (2000) Mechanisms of transcriptional regulation by Runt domain proteins. Semin Cell Dev Biol 11:369-375. (Pubitemid 32096086)
78. Ovcharenko I, Nobrega MA (2005) Identifying synonymous regulatory elements in vertebrate genomes. Nucleic Acids Res 33:W403-W407. (Pubitemid 44529952)
79. Lin YC, et al. (2010) A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol 11:635-643.
80. Osato M (2004) Point mutations in the RUNX1/AML1 gene: Another actor in RUNX leukemia. Oncogene 23:4284-4296.
81. Chapuis N, et al. (2010) IκB kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in acute myeloid leukemia. Blood 116:4240-4250.
82. Zhou FL, et al. (2010) Involvement of oxidative stress in the relapse of acute myeloid leukemia. J Biol Chem 285:15010-15015.
83. Kato M, et al. (2003) Superoxide radical generation and Mn- and Cu-Zn superoxide dismutases activities in human leukemic cells. Hematol Oncol 21:11-16. (Pubitemid 36356240)
84. Guzman ML, et al. (2001) Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 98:2301-2307.
85. Schneider BP, et al. (2008) Triple-negative breast cancer: Risk factors to potential targets. Clin Cancer Res 14:8010-8018.
86. Fang J, Seki T, Maeda H (2009) Therapeutic strategies by modulating oxygen stress in cancer and inflammation. Adv Drug Deliv Rev 61:290-302.
87. Moffat J, et al. (2006) A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124:1283-1298.
88. Miller-Jensen K, Janes KA, Brugge JS, Lauffenburger DA (2007) Common effector processing mediates cell-specific responses to stimuli. Nature 448:604-608. (Pubitemid 47206933)
89. Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS (2007) Quantifying similarity between motifs. Genome Biol 8:R24.
90. Sheskin DJ (2007) Handbook of Parametric and Nonparametric Statistical Procedures (Chapman & Hall, New York), 4th Ed.
91. Melnikova IN, Crute BE, Wang S, Speck NA (1993) Sequence specificity of the corebinding factor. J Virol 67:2408-2411.