TGF-β1 interactome: Metastasis and beyond

Cancer Genomics and Proteomics

Volumn 7, Issue 4, 2010, Pages 217-229

  Perera, M ^a   Tsang, C S ^a,d   Distel, R J ^b   Lacy, J N ^b   Ohno Machado, L ^c   Ricchiuti, V ^b   Samaranayake, L P ^a   Smejkal, G B ^b   Smith, M G ^c   Trachtenberg, A J ^b   Kuo, Winston Patrick ^b,e  

^a UNIVERSITY OF HONG KONG   (Hong Kong)

^b HARVARD MEDICAL SCHOOL   (United States)

^c FLORIDA HOSPITAL   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e HARVARD SCHOOL OF DENTAL MEDICINE   (United States)

Author keywords

Diagnostics; Interactome; Metastatsis; Review; Therapeutics; Transforming growth factor 1

Indexed keywords

HISTONE ACETYLTRANSFERASE PCAF; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; SMAD7 PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA1; PROTEOME;

ANGIOGENESIS; CANCER GROWTH; CANCER INVASION; CARCINOGENESIS; EPITHELIAL MESENCHYMAL TRANSITION; FUNCTIONAL PROTEOMICS; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE MAPPING; GENETIC CODE; IMMUNOSUPPRESSIVE TREATMENT; METASTASIS; NEOPLASM; NONHUMAN; POLARIZATION; PROTEIN DNA INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; NEOVASCULARIZATION (PATHOLOGY); VASCULARIZATION;

ANIMALS; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEOME; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA1;

EID: 77955947596     PISSN: 11096535     EISSN: 17906245     Source Type: Journal    
DOI: None     Document Type: Review

References (128)

1. Hanahan D and Weinberg RA: The hallmarks of cancer. Cell 100: 57-70, 2000.
2. Nakai M, Takauchi S, Yamaguchi T, Kawamata T, Maeda K and Tanaka C: Establishment of a murine model for metastasis of cytokine-producing tumor to the brain. Pigment Cell Res 10: 304-309, 1997.
3. Massague J, Blain SW and Lo RS: TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 103: 295-309, 2000.
4. Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW and Waltham M: Vimentin and epithelial-mesenchymal transition in human breast cancer - observations in vitro and in vivo. Cells Tissues Organs 185: 191-203, 2007.
5. Nakajima S, Doi R, Toyoda E, Tsuji S, Wada M, Koizumi M, Tulachan SS, Ito D, Kami K, Mori T, Kawaguchi Y, Fujimoto K, Hosotani R and Imamura M: N-Cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. Clin Cancer Res 10: 4125-4133, 2004.
6. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C and Roberts AB: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1: 260-266, 1999.
7. Dunker N and Krieglstein K: Targeted mutations of transforming growth factor-beta genes reveal important roles in mouse development and adult homeostasis. Eur J Biochem 267: 6982-6988, 2000.
8. Safina A, Ren MQ, Vandette E and Bakin AV: TAK1 is required for TGF-beta 1-mediated regulation of matrix metalloproteinase-9 and metastasis. Oncogene 27: 1198-1207, 2008.
9. Sinpitaksakul SN, Pimkhaokham A, Sanchavanakit N and Pavasant P: TGF-beta1-induced MMP-9 expression in HNSCC cell lines via Smad/MLCK pathway. Biochem Biophys Res Commun 371: 713-718, 2008.
10. Roberts AB and Wakefield LM: The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 100: 8621-8623, 2003.
11. de Caestecker MP, Piek E and Roberts AB: Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst 92: 1388-1402, 2000.
12. Koli K, Saharinen J, Hyytiainen M, Penttinen C and Keski-Oja J: Latency, activation, and binding proteins of TGF-beta. Microsc Res Tech 52: 354-362, 2001.
13. Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425: 577-584, 2003.
14. Roberts AB: Molecular and cell biology of TGF-beta. Miner Electrolyte Metab 24: 111-119, 1998.
15. de Caestecker M: The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev 15: 1-11, 2004.
16. Feng XH and Derynck R: Specificity and versatility in TGF-beta signaling through Smads. Annu Rev Cell Dev Biol 21: 659-693, 2005.
17. Wrana JL, Attisano L, Wieser R, Ventura F and Massague J: Mechanism of activation of the TGF-beta receptor. Nature 370: 341-347, 1994.
18. Huse M, Chen YG, Massague J and Kuriyan J: Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12. Cell 96: 425-436, 1999.
19. Sehgal I and Thompson TC: Novel regulation of type IV collagenase (matrix metalloproteinase-9 and -2) activities by transforming growth factor-beta1 in human prostate cancer cell lines. Mol Biol Cell 10: 407-416, 1999.
20. Uttamsingh S, Bao X, Nguyen KT, Bhanot M, Gong J, Chan JL, Liu F, Chu TT and Wang LH: Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene 27: 2626-2634, 2008.
21. Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I and Wrana JL: High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307: 1621-1625, 2005.
22. Souchelnytskyi S: Proteomics of TGF-beta signaling and its impact on breast cancer. Expert Rev Proteomics 2: 925-935, 2005.
23. Datta PK, Chytil A, Gorska AE and Moses HL: Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling. J Biol Chem 273: 34671-34674, 1998.
24. Charng MJ, Zhang D, Kinnunen P and Schneider MD: A novel protein distinguishes between quiescent and activated forms of the type I transforming growth factor beta receptor. J Biol Chem 273: 9365-9368, 1998.
25. Wang T, Donahoe PK and Zervos AS: Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12. Science 265: 674-676, 1994.
26. Yi JY, Shin I and Arteaga CL: Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. J Biol Chem 280: 10870-10876, 2005.
27. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K and ten Dijke P: TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J 16: 5353-5362, 1997.
28. Wu MY and Hill CS: Tgf-beta superfamily signaling in embryonic development and homeostasis. Dev Cell 16: 329-343, 2009.
29. Gorsch SM, Memoli VA, Stukel TA, Gold LI and Arrick BA: Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res 52: 6949-6952, 1992.
30. Saito H, Tsujitani S, Oka S, Kondo A, Ikeguchi M, Maeta M and Kaibara N: An elevated serum level of transforming growth factor-beta 1 (TGF-beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res 20: 4489-4493, 2000.
31. Welch DR, Fabra A and Nakajima M: Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci USA 87: 7678-7682, 1990.
32. Glick AB, Lee MM, Darwiche N, Kulkarni AB, Karlsson S and Yuspa SH: Targeted deletion of the TGF-beta 1 gene causes rapid progression to squamous cell carcinoma. Genes Dev 8: 2429-2440, 1994.
33. Cui W, Fowlis DJ, Bryson S, Duffle E, Ireland H, Balmain A and Akhurst RJ: TGFbeta1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86: 531-542, 1996.
34. Weeks BH, He W, Olson KL and Wang XJ: Inducible expression of transforming growth factor beta 1 in papillomas causes rapid metastasis. Cancer Res 61: 7435-7443, 2001.
35. Eisma RJ, Spiro JD, von Biberstein SE, Lindquist R and Kreutzer DL: Decreased expression of transforming growth factor beta receptors on head and neck squamous cell carcinoma tumor cells. Am J Surg 172: 641-645, 1996.
36. Abe T, Ouyang H, Migita T, Kato Y, Kimura M, Shiiba K, Sunamura M, Matsuno S and Horii A: The somatic mutation frequency of the transforming growth factor beta receptor type II gene varies widely among different cancers with microsatellite instability. Eur J Surg Oncol 22: 474-477, 1996.
37. Maitra A, Molberg K, Albores-Saavedra J and Lindberg G: Loss of Dpc4 expression in colonic adenocarcinomas correlates with the presence of metastatic disease. Am J Pathol 157: 1105-1111, 2000.
38. Barcellos-Hoff MH: Integrative radiation carcinogenesis: interactions between cell and tissue responses to DNA damage. Semin Cancer Biol 15: 138-148, 2005.
39. Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2: 442-454, 2002.
40. Miettinen PJ, Ebner R, Lopez AR and Derynck R: TGF-beta-induced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J Cell Biol 127: 2021-2036, 1994.
41. Oft M, Peli J, Rudaz C, Schwarz H, Beug H and Reichmann E: TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 10: 2462-2477, 1996.
42. Derynck R and Akhurst RJ: Differentiation plasticity regulated by TGF-beta family proteins in development and disease. Nat Cell Biol 9: 1000-1004, 2007.
43. Portella G, Cumming SA, Liddell J, Cui W, Ireland H, Akhurst RJ and Balmain A: Transforming growth factor beta is essential for spindle cell conversion of mouse skin carcinoma in vivo: implications for tumor invasion. Cell Growth Differ 9: 393-404, 1998.
44. Oft M, Heider KH and Beug H: TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol 8: 1243-1252, 1998.
45. Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH and Moustakas A: HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to- mesenchymal transition. J Biol Chem 283: 33437-33446, 2008.
46. Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y and Wrana JL: Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 307: 1603-1609, 2005.
47. Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J and Nieto MA: Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 21: 3241-3246, 2002.
48. Xie L, Law BK, Chytil AM, Brown KA, Aakre ME and Moses HL: Activation of the Erk pathway is required for TGF-beta 1-induced EMT in vitro. Neoplasia 6: 603-610, 2004.
49. Xu J, Lamouille S and Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res 19: 156-172, 2009.
50. Zavadil J, Cermak L, Soto-Nieves N and Bottinger EP: Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. Embo J 23: 1155-1165, 2004.
51. Willis BC and Borok Z: TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am J Physiol Lung Cell Mol Physiol 293: L525-534, 2007.
52. Fuchs IB, Lichtenegger W, Buehler H, Henrich W, Stein H, Kleine-Tebbe A and Schaller G: The prognostic significance of epithelial-mesenchymal transition in breast cancer. Anticancer Res 22: 3415-3419, 2002.
53. Sato M, Muragaki Y, Saika S, Roberts AB and Ooshima A: Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112: 1486-1494, 2003.
54. Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL and Arteaga CL: Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 275: 36803-36810, 2000.
55. Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, Arteaga CL and Moses HL: Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 12: 27-36, 2001.
56. Edlund S, Landstrom M, Heldin CH and Aspenstrom P: Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA. Mol Biol Cell 13: 902-914, 2002.
57. Bergers G and Benjamin LE: Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3: 401-410, 2003.
58. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA and Massague J: A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537-549, 2003.
59. Merwin JR, Anderson JM, Kocher O, Van Itallie CM and Madri JA: Transforming growth factor beta 1 modulates extracellular matrix organization and cell-cell junctional complex formation during in vitro angiogenesis. J Cell Physiol 142: 117-128, 1990.
60. Yang EY and Moses HL: Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane. J Cell Biol 111: 731-741, 1990.
61. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S and Akhurst RJ: Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121: 1845-1854, 1995.
62. Oshima M, Oshima H and Taketo MM: TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol 179: 297-302, 1996.
63. Sanchez-Eisner T, Botella LM, Velasco B, Corbi A, Attisano L and Bernabeu C: Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem 276: 38527-38535, 2001.
64. Hasegawa Y, Takanashi S, Kanehira Y, Tsushima T, Imai T and Okumura K: Transforming growth factor-beta 1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer 91: 964-971, 2001.
65. Steams ME, Garcia FU, Fudge K, Rhim J and Wang M: Role of interleukin 10 and transforming growth factor beta 1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice. Clin Cancer Res 5: 711-720, 1999.
66. Mira E, Lacalle RA, Buesa JM, de Buitrago GG, Jimenez-Baranda S, Gomez-Mouton C, Martinez AC and Manes S: Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface. J Cell Sci 117: 1847-1857, 2004.
67. van Kempen LC and Coussens LM: MMP9 potentiates pulmonary metastasis formation. Cancer Cell 2: 251-252, 2002.
68. Derynck R, Akhurst RJ and Balmain A: TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29: 117-129, 2001.
69. Hagedorn HG, Bachmeier BE and Nerlich AG: Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-beta in invasive carcinomas (Review). Int J Oncol 18: 669-681, 2001.
70. Yamaguchi T and Sakaguchi S: Regulatory T-cells in immune surveillance and treatment of cancer. Semin Cancer Biol 16: 115-123, 2006.
71. Torre-Amione G, Beauchamp RD, Koeppen H, Park BH, Schreiber H, Moses HL and Rowley DA: A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance. Proc Natl Acad Sci USA 87: 1486-1490, 1990.
72. Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM and Forbes JT: Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. J Clin Invest 92: 2569-2576, 1993.
73. Akhurst RJ and Derynck R: TGF-beta signaling in cancer - a double-edged sword. Trends Cell Biol 11: S44-51, 2001.
74. Geiser AG, Letterio JJ, Kulkarni AB, Karlsson S, Roberts AB and Sporn MB: Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype. Proc Natl Acad Sci USA 90: 9944-9948, 1993.
75. Letterio JJ and Roberts AB: Regulation of immune responses by TGF-beta. Annu Rev Immunol 16: 137-161, 1998.
76. Tucker RF, Shipley GD, Moses HL and Holley RW: Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science 226: 705-707, 1984.
77. Arteaga CL, Coffey RJ Jr, Dugger TC, McCutchen CM, Moses HL and Lyons RM: Growth stimulation of human breast cancer cells with anti-transforming growth factor beta antibodies: evidence for negative autocrine regulation by transforming growth factor beta. Cell Growth Differ 1: 367-374, 1990.
78. Wu SP, Sun LZ, Willson JK, Humphrey L, Kerbel R and Brattain MG: Repression of autocrine transforming growth factor beta 1 and beta 2 in quiescent CBS colon carcinoma cells leads to progression of tumorigenic properties. Cell Growth Differ 4: 115-123, 1993.
79. Lu SL, Zhang WC, Akiyama Y, Nomizu T and Yuasa Y: Genomic structure of the transforming growth factor beta type II receptor gene and its mutations in hereditary nonpolyposis colorectal cancers. Cancer Res 56: 4595-4598, 1996.
80. Guasch G, Schober M, Pasolli HA, Conn EB, Polak L and Fuchs E: Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 12: 313-327, 2007.
81. Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, Wang J, Gentry LE, Wang XF and Brattain MG: Expression of transforming growth factor beta type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem 269: 26449-26455, 1994.
82. Turco A, Coppa A, Aloe S, Baccheschi G, Morrone S, Zupi G and Colletta G: Overexpression of transforming growth factor beta-type II receptor reduces tumorigenicity and metastastic potential of K-ras-transformed thyroid cells. Int J Cancer 80: 85-91, 1999.
83. Pardali K, Kurisaki A, Moren A, ten Dijke P, Kardassis D and Moustakas A: Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta. J Biol Chem 275: 29244-29256, 2000.
84. Rich JN, Zhang M, Datto MB, Bigner DD and Wang XF: Transforming growth factor-beta-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines. J Biol Chem 274: 35053-35058, 1999.
85. Boyer Arnold N and Korc M: Smad7 abrogates transforming growth factor-beta1-mediated growth inhibition in COLO-357 cells through functional inactivation of the retinoblastoma protein. J Biol Chem 280: 21858-21866, 2005.
86. Han SU, Kim HT, Seong DH, Kim YS, Park YS, Bang YJ, Yang HK and Kim SJ: Loss of the Smad3 expression increases susceptibility to tumorigenicity in human gastric cancer. Oncogene 23: 1333-1341, 2004.
87. Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW and Vogelstein B: Mad-related genes in the human. Nat Genet 13: 347-349, 1996.
88. 88 Uchida K, Nagatake M, Osada H, Yatabe Y, Kondo M, Mitsudomi T, Masuda A and Takahashi T: Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer Res 56: 5583-5585, 1996. (Pubitemid 26422155)
89. Wolfraim LA, Fernandez TM, Mamura M, Fuller WL, Kumar R, Cole DE, Byfield S, Felici A, Flanders KC, Walz TM, Roberts AB, Aplan PD, Balis FM and Letterio JJ: Loss of Smad3 in acute T-cell lymphoblastic leukemia. N Engl J Med 351: 552-559, 2004.
90. Luttges J, Galehdari H, Brocker V, Schwarte-Waldhoff I, Henne-Bruns D, Kloppel G, Schmieget W and Hahn SA: Allelic loss is often the first hit in the biallelic inactivation of the p53 and DPC4 genes during pancreatic carcinogenesis. Am J Pathol 158: 1677-1683, 2001.
91. Xu X, Brodie SG, Yang X, Im YH, Parks WT, Chen L, Zhou YX, Weinstein M, Kim SJ and Deng CX: Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 19: 1868-1874, 2000.
92. Kleeff J, Ishiwata T, Maruyama H, Friess H, Truong P, Buchler MW, Falb D and Korc M: The TGF-beta signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer. Oncogene 18: 5363-5372, 1999.
93. Xie W, Bharathy S, Kim D, Haffty BG, Rimm DL and Reiss M: Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis. Oncol Res 14: 61-73, 2003.
94. Xie W, Rimm DL, Lin Y, Shih WJ and Reiss M: Loss of Smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis. Cancer J 9: 302-312, 2003.
95. Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, de Caestecker MP, Danielpour D, Book-Melamed N, Timberg R, Duckett CS, Lechleider RJ, Steller H, Orly J, Kim SJ and Roberts AB: A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol 2: 915-921, 2000.
96. Edlund S, Bu S, Schuster N, Aspenstrom P, Heuchel R, Heldin NE, ten Dijke P, Heldin CH and Landstrom M: Transforming growth factor-beta1 (TGF-beta)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-beta-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell 14: 529-544, 2003.
97. Kim KY, Kim BC, Xu Z and Kim SJ: Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells. J Biol Chem 279: 29478-29484, 2004.
98. Kamaraju AK and Roberts AB: Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. J Biol Chem 280: 1024-1036, 2005.
99. Yu L, Hebert MC and Zhang YE: TGF-beta receptor-activated p38 MAP kinase mediates Smad-independent TGF-beta responses. Embo J 21: 3749-3759, 2002.
100. Moustakas A and Heldin CH: Non-Smad TGF-beta signals. J Cell Sci 118: 3573-3584, 2005.
101. Yagi K, Furuhashi M, Aoki H, Goto D, Kuwano H, Sugamura K, Miyazono K and Kato M: c-myc is a downstream target of the Smad pathway. J Biol Chem 277: 854-861, 2002.
102. Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, Munger K, Howley PM and Moses HL: TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell 61: 777-785, 1990.
103. He J, Tegen SB, Krawitz AR, Martin GS and Luo K: The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins. J Biol Chem 278: 30540-30547, 2003.
104. Heldin CH: Development and possible clinical use of antagonists for PDGF and TGF-beta. Ups J Med Sci 109: 165-178, 2004.
105. Park JA, Wang E, Kurt RA, Schluter SF, Hersh EM and Akporiaye ET: Expression of an antisense transforming growth factor-beta 1 transgene reduces tumorigenicity of EMT6 mammary tumor cells. Cancer Gene Ther 4: 42-50, 1997.
106. Seon BK, Matsuno F, Haruta Y, Kondo M and Barcos M: Long-lasting complete inhibition of human solid tumors in SCID mice by targeting endothelial cells of tumor vasculature with antihuman endoglin immunotoxin. Clin Cancer Res 3: 1031-1044, 1997.
107. Wojtowicz-Praga S, Verma UN, Wakefield L, Esteban JM, Hartmann D and Mazumder A: Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2. J Immunother Emphasis Tumor Immunol 19: 169-175, 1996.
108. Platten M, Wild-Bode C, Wick W, Leitlein J, Dichgans J and Weiler M: N-[3,4-Dimethoxycinnamoyl]-anthranilic acid (tranilast) inhibits transforming growth factor-beta relesase and reduces migration and invasiveness of human malignant glioma cells. Int J Cancer 93: 53-61, 2001.
109. Callahan JF, Burgess JL, Fornwald JA, Gaster LM, Harling JD, Harrington FP, Heer J, Kwon C, Lehr R, Mathur A, Olson BA, Weinstock J and Laping NJ: Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem 45: 999-1001, 2002.
110. Yingling JM, Blanchard KL and Sawyer JS: Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3: 1011-1022, 2004.
111. Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee WC, Pontz T, Corbley MJ, Cheung HK, Arduini RM, Mead JN, Newman MN, Papadatos JL, Bowes S, Josiah S and Ling LE: Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFbeta receptor kinase (TbetaRI). Bioorg Med Chem Lett 13: 4355-4359, 2003.
112. Ge R, Rajeev V, Subramanian G, Reiss KA, Liu D, Higgins L, Joly A, Dugar S, Chakravarty J, Henson M, McEnroe G, Schreiner G and Reiss M: Selective inhibitors of type I receptor kinase block cellular transforming growth factor-beta signaling. Biochem Pharmacol 68: 41-50, 2004.
113. Peng SB, Yan L, Xia X, Watkins SA, Brooks HB, Beight D, Herron DK, Jones ML, Lampe JW, McMillen WT, Mort N, Sawyer JS and Yingling JM: Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry 44: 2293-2304, 2005.
114. Subramanian G, Schwarz RE, Higgins L, McEnroe G, Chakravarty S, Dugar S and Reiss M: Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res 64: 5200-5211, 2004.
115. Dorigo O, Shawler DL, Royston I, Sobol RE, Berek JS and Fakhrai H: Combination of transforming growth factor beta antisense and interleukin-2 gene therapy in the murine ovarian teratoma model. Gynecol Oncol 71: 204-210, 1998.
116. Wu RS, Kobie JJ, Besselsen DG, Fong TC, Mack VD, McEarchern JA and Akporiaye ET: Comparative analysis of IFN-gamma B7.1 and antisense TGF-beta gene transfer on the tumorigenicity of a poorly immunogenic metastatic mammary carcinoma. Cancer Immunol Immunother 50: 229-240, 2001.
117. Fakhrai H, Dorigo O, Shawler DL, Lin H, Mercola D, Black KL, Royston I and Sobol RE: Eradication of established intracranial rat gliomas by transforming growth factor beta antisense gene therapy. Proc Natl Acad Sci USA 93: 2909-2914, 1996.
118. Kobie JJ, Wu RS, Kurt RA, Lou S, Adelman MK, Whitesell LJ, Ramanathapuram LV, Arteaga CL and Akporiaye ET: Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 63: 1860-1864, 2003.
119. Liau LM, Fakhrai H and Black KL: Prolonged survival of rats with intracranial C6 gliomas by treatment with TGF-beta antisense gene. Neurol Res 20: 742-747, 1998.
120. Maggard M, Meng L, Ke B, Allen R, Devgan L and Imagawa DK: Antisense TGF-beta2 immunotherapy for hepatocellular carcinoma: treatment in a rat tumor model. Ann Surg Oncol 8: 32-37, 2001.
121. Hau P, Jachimczak P, Schlingensiepen R, Schulmeyer F, Jauch T, Steinbrecher A, Brawanski A, Proescholdt M, Schlaier J, Buchroithner J, Pichler J, Wurm G, Mehdorn M, Strege R, Schuierer G, Villarrubia V, Fellner F, Jansen O, Straube T, Nohria V, Goldbrunner M, Kunst M, Schmaus S, Stauder G, Bogdahn U and Schlingensiepen KH: Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies. Oligonucleotides 17: 201-212, 2007.
122. Hoefer M and Anderer FA: Anti-(transforming growth factor beta) antibodies with predefined specificity inhibit metastasis of highly tumorigenic human xenotransplants in nu/nu mice. Cancer Immunol Immunother 41: 302-308, 1995.
123. Akhurst RJ: Large- and small-molecule inhibitors of transforming growth factor-beta signaling. Curr Opin Investig Drugs 7: 513-521, 2006.
124. Yin JJ, Seiander K, Chirgwin JM, Dallas M, Grubbs BG, Wieser R, Massague J, Mundy GR and Guise TA: TGF-beta signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J Clin Invest 103: 197-206, 1999.
125. Gorelik L and Flavell RA: Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T-cells. Nat Med 7: 1118-1122, 2001.
126. Shah AH, Tabayoyong WB, Kundu SD, Kim SJ, Van Parijs L, Liu VC, Kwon E, Greenberg NM and Lee C: Suppression of tumor metastasis by blockade of transforming growth factor beta signaling in bone marrow cells through a retroviral-mediated gene therapy in mice. Cancer Res 62: 7135-7138, 2002.
127. Uhl M, Aulwurm S, Wischhusen J, Weiler M, Ma JY, Almirez R, Mangadu R, Liu YW, Platten M, Herrlinger U, Murphy A, Wong DH, Wick W, Higgins LS and Weiler M: SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res 64: 7954-7961, 2004.
128. Inman GJ, Nicolas FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ and Hill CS: SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol Pharmacol 62: 65-74, 2002.