Roles of TGFβ signaling Smads in squamous cell carcinoma

Cell and Bioscience

Volumn 1, Issue 1, 2011, Pages

  Han, Gangwen ^a   Wang, Xiao Jing ^a  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

Author keywords

Smad2; Smad3; Smad4; Squamous cell carcinomas; TGF signaling

Indexed keywords

ANIMALIA;

EID: 84862900400     PISSN: None     EISSN: 20453701     Source Type: Journal    
DOI: 10.1186/2045-3701-1-41     Document Type: Review

References (76)

1. Feng XH, Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol 2005, 21:659-693. 10.1146/annurev.cellbio.21.022404.142018, 16212511.
2. Liu T, Feng XH. Regulation of TGF-beta signalling by protein phosphatases. The Biochemical journal 2010, 430(2):191-198. 10.1042/BJ20100427, 3154754, 20704570.
3. Li AG, Lu SL, Han G, Kulesz-Martin M, Wang XJ. Current view of the role of transforming growth factor beta 1 in skin carcinogenesis. J Investig Dermatol Symp Proc 2005, 10(2):110-117. 10.1111/j.1087-0024.2005.200403.x, 16363062.
4. Padua D, Massague J. Roles of TGFbeta in metastasis. Cell research 2009, 19(1):89-102. 10.1038/cr.2008.316, 19050696.
5. Harradine KA, Akhurst RJ. Mutations of TGFbeta signaling molecules in human disease. Annals of medicine 2006, 38(6):403-414. 10.1080/07853890600919911, 17008304.
6. Slattery ML, Herrick JS, Lundgreen A, Wolff RK. Genetic variation in the TGF-beta signaling pathway and colon and rectal cancer risk. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2011, 20(1):57-69.
7. Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S, Andrulis IL, et al. MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 1996, 86(4):543-552. 10.1016/S0092-8674(00)80128-2, 8752209.
8. Uchida K, Nagatake M, Osada H, Yatabe Y, Kondo M, Mitsudomi T, Masuda A, Takahashi T. Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cancer Res 1996, 56(24):5583-5585.
9. Yakicier MC, Irmak MB, Romano A, Kew M, Ozturk M. Smad2 and Smad4 gene mutations in hepatocellular carcinoma. Oncogene 1999, 18(34):4879-4883. 10.1038/sj.onc.1202866, 10490821.
10. Papadimitrakopoulou VA, Oh Y, El-Naggar A, Izzo J, Clayman G, Mao L. Presence of multiple incontiguous deleted regions at the long arm of chromosome 18 in head and neck cancer. Clinical cancer research: an official journal of the American Association for Cancer Research 1998, 4(3):539-544.
11. Snijders AM, Schmidt BL, Fridlyand J, Dekker N, Pinkel D, Jordan RC, Albertson DG. Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma. Oncogene 2005, 24(26):4232-4242. 10.1038/sj.onc.1208601, 15824737.
12. Takebayashi S, Ogawa T, Jung KY, Muallem A, Mineta H, Fisher SG, Grenman R, Carey TE. Identification of new minimally lost regions on 18q in head and neck squamous cell carcinoma. Cancer research 2000, 60(13):3397-3403.
13. Qiu W, Schonleben F, Li X, Su GH. Disruption of transforming growth factor beta-Smad signaling pathway in head and neck squamous cell carcinoma as evidenced by mutations of SMAD2 and SMAD4. Cancer letters 2007, 245(1-2):163-170. 10.1016/j.canlet.2006.01.003, 1741856, 16478646.
14. Hoot KE, Lighthall J, Han G, Lu SL, Li A, Ju W, Kulesz-Martin M, Bottinger E, Wang XJ. Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. The Journal of clinical investigation 2008, 118(8):2722-2732. 2447925, 18618014.
15. Guasch G, Schober M, Pasolli HA, Conn EB, Polak L, Fuchs E. Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia. Cancer Cell 2007, 12(4):313-327. 10.1016/j.ccr.2007.08.020, 2424201, 17936557.
16. Maliekal TT, Antony ML, Nair A, Paulmurugan R, Karunagaran D. Loss of expression, and mutations of Smad 2 and Smad 4 in human cervical cancer. Oncogene 2003, 22(31):4889-4897. 10.1038/sj.onc.1206806, 12894231.
17. Muro-Cacho CA, Rosario-Ortiz K, Livingston S, Munoz-Antonia T. Defective transforming growth factor beta signaling pathway in head and neck squamous cell carcinoma as evidenced by the lack of expression of activated Smad2. Clin Cancer Res 2001, 7(6):1618-1626.
18. Xie W, Bharathy S, Kim D, Haffty BG, Rimm DL, Reiss M. Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis. Oncology research 2003, 14(2):61-73.
19. Waldrip WR, Bikoff EK, Hoodless PA, Wrana JL, Robertson EJ. Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell 1998, 92(6):797-808. 10.1016/S0092-8674(00)81407-5, 9529255.
20. Weinstein M, Yang X, Li C, Xu X, Gotay J, Deng CX. Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2. Proceedings of the National Academy of Sciences of the United States of America 1998, 95(16):9378-9383. 10.1073/pnas.95.16.9378, 21346, 9689088.
21. Heyer J, Escalante-Alcalde D, Lia M, Boettinger E, Edelmann W, Stewart CL, Kucherlapati R. Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 1999, 96(22):12595-12600. 10.1073/pnas.96.22.12595, 23005, 10535967.
22. Nomura M, Li E. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 1998, 393(6687):786-790. 10.1038/31693, 9655392.
23. Ju W, Ogawa A, Heyer J, Nierhof D, Yu L, Kucherlapati R, Shafritz DA, Bottinger EP. Deletion of Smad2 in mouse liver reveals novel functions in hepatocyte growth and differentiation. Molecular and cellular biology 2006, 26(2):654-667. 10.1128/MCB.26.2.654-667.2006, 1346892, 16382155.
24. Hamamoto T, Beppu H, Okada H, Kawabata M, Kitamura T, Miyazono K, Kato M. Compound disruption of smad2 accelerates malignant progression of intestinal tumors in apc knockout mice. Cancer research 2002, 62(20):5955-5961.
25. Tannehill-Gregg SH, Kusewitt DF, Rosol TJ, Weinstein M. The roles of Smad2 and Smad3 in the development of chemically induced skin tumors in mice. Vet Pathol 2004, 41(3):278-282. 10.1354/vp.41-3-278, 15133179.
26. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009, 19(2):156-172. 10.1038/cr.2009.5, 19153598.
27. Ikushima H, Miyazono K. TGFbeta signalling: a complex web in cancer progression. Nature reviews Cancer 2010, 10(6):415-424. 10.1038/nrc2853, 20495575.
28. Lebrin F, Deckers M, Bertolino P, Ten Dijke P. TGF-beta receptor function in the endothelium. Cardiovascular research 2005, 65(3):599-608. 10.1016/j.cardiores.2004.10.036, 15664386.
29. Tian M, Neil JR, Schiemann WP. Transforming growth factor-beta and the hallmarks of cancer. Cellular signalling 2011, 23(6):951-962. 10.1016/j.cellsig.2010.10.015, 20940046.
30. Hoot KE, Oka M, Han G, Bottinger E, Zhang Q, Wang XJ. HGF upregulation contributes to angiogenesis in mice with keratinocyte-specific Smad2 deletion. J Clin Invest 2010, 120(10):3606-3616. 10.1172/JCI43304, 2947237, 20852387.
31. Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Current opinion in cell biology 2005, 17(5):548-558. 10.1016/j.ceb.2005.08.001, 16098727.
32. Massague J, Gomis RR. The logic of TGFbeta signaling. FEBS Lett 2006, 580(12):2811-2820. 10.1016/j.febslet.2006.04.033, 16678165.
33. Piek E, Moustakas A, Kurisaki A, Heldin CH, ten Dijke P. TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. Journal of cell science 1999, 112(Pt 24):4557-4568.
34. Valcourt U, Kowanetz M, Niimi H, Heldin CH, Moustakas A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Molecular biology of the cell 2005, 16(4):1987-2002. 10.1091/mbc.E04-08-0658, 1073677, 15689496.
35. Benvenuti S, Comoglio PM. The MET receptor tyrosine kinase in invasion and metastasis. Journal of cellular physiology 2007, 213(2):316-325. 10.1002/jcp.21183, 17607709.
36. Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini L, Gaudino G, Tamagnone L, Coffer A, Comoglio PM. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. The Journal of cell biology 1992, 119(3):629-641. 10.1083/jcb.119.3.629, 2289675, 1383237.
37. van de Laar IM, Oldenburg RA, Pals G, Roos-Hesselink JW, de Graaf BM, Verhagen JM, Hoedemaekers YM, Willemsen R, Severijnen LA, Venselaar H, et al. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis. Nature genetics 2011, 43(2):121-126. 10.1038/ng.744, 21217753.
38. Regalado ES, Guo DC, Villamizar C, Avidan N, Gilchrist D, McGillivray B, Clarke L, Bernier F, Santos-Cortez RL, Leal SM, et al. Exome Sequencing Identifies SMAD3 Mutations as a Cause of Familial Thoracic Aortic Aneurysm and Dissection With Intracranial and Other Arterial Aneurysms. Circulation research 2011, 109(6):680-686. 10.1161/CIRCRESAHA.111.248161, 21778426.
39. Ku JL, Park SH, Yoon KA, Shin YK, Kim KH, Choi JS, Kang HC, Kim IJ, Han IO, Park JG. Genetic alterations of the TGF-beta signaling pathway in colorectal cancer cell lines: a novel mutation in Smad3 associated with the inactivation of TGF-beta-induced transcriptional activation. Cancer letters 2007, 247(2):283-292. 10.1016/j.canlet.2006.05.008, 16828225.
40. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314(5797):268-274. 10.1126/science.1133427, 16959974.
41. Tram E, Ibrahim-Zada I, Briollais L, Knight JA, Andrulis IL, Ozcelik H. Identification of germline alterations of the mad homology 2 domain of SMAD3 and SMAD4 from the Ontario site of the breast cancer family registry (CFR). Breast cancer research: BCR 2011, 13(4):R77. 10.1186/bcr2926, 3236341, 21835029.
42. Riggins GJ, Kinzler KW, Vogelstein B, Thiagalingam S. Frequency of Smad gene mutations in human cancers. Cancer research 1997, 57(13):2578-2580.
43. Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, et al. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 2011, 333(6046):1154-1157. 10.1126/science.1206923, 3162986, 21798897.
44. Mhawech-Fauceglia P, Kesterson J, Wang D, Akers S, Dupont NC, Clark K, Lele S, Liu S. Expression and clinical significance of the transforming growth factor-beta signalling pathway in endometrial cancer. Histopathology 2011, 59(1):63-72. 10.1111/j.1365-2559.2011.03892.x, 21771027.
45. Han SU, Kim HT, Seong DH, Kim YS, Park YS, Bang YJ, Yang HK, Kim SJ. Loss of the Smad3 expression increases susceptibility to tumorigenicity in human gastric cancer. Oncogene 2004, 23(7):1333-1341. 10.1038/sj.onc.1207259, 14647420.
46. Wolfraim LA, Fernandez TM, Mamura M, Fuller WL, Kumar R, Cole DE, Byfield S, Felici A, Flanders KC, Walz TM, et al. Loss of Smad3 in acute T-cell lymphoblastic leukemia. The New England journal of medicine 2004, 351(6):552-559. 10.1056/NEJMoa031197, 15295048.
47. Millet C, Zhang YE. Roles of Smad3 in TGF-beta signaling during carcinogenesis. Critical reviews in eukaryotic gene expression 2007, 17(4):281-293. 2639747, 17725494.
48. Bae DS, Blazanin N, Licata M, Lee J, Glick AB. Tumor suppressor and oncogene actions of TGFbeta1 occur early in skin carcinogenesis and are mediated by Smad3. Molecular carcinogenesis 2009, 48(5):441-453. 10.1002/mc.20482, 2730634, 18942075.
49. Vijayachandra K, Lee J, Glick AB. Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model. Cancer research 2003, 63(13):3447-3452.
50. Yang YA, Zhang GM, Feigenbaum L, Zhang YE. Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer cell 2006, 9(6):445-457. 10.1016/j.ccr.2006.04.025, 2708973, 16766264.
51. Zhu Y, Richardson JA, Parada LF, Graff JM. Smad3 mutant mice develop metastatic colorectal cancer. Cell 1998, 94(6):703-714. 10.1016/S0092-8674(00)81730-4, 9753318.
52. Datto MB, Frederick JP, Pan L, Borton AJ, Zhuang Y, Wang XF. Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Molecular and cellular biology 1999, 19(4):2495-2504. 84042, 10082515.
53. Yang X, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. The EMBO journal 1999, 18(5):1280-1291. 10.1093/emboj/18.5.1280, 1171218, 10064594.
54. Maggio-Price L, Treuting P, Zeng W, Tsang M, Bielefeldt-Ohmann H, Iritani BM. Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice. Cancer research 2006, 66(2):828-838. 10.1158/0008-5472.CAN-05-2448, 16424015.
55. Li AG, Lu SL, Zhang MX, Deng C, Wang XJ. Smad3 knockout mice exhibit a resistance to skin chemical carcinogenesis. Cancer research 2004, 64(21):7836-7845. 10.1158/0008-5472.CAN-04-1331, 15520189.
56. Patamalai B, Burow DL, Gimenez-Conti I, Zenklusen JC, Conti CJ, Klein-Szanto AJ, Fischer SM. Altered expression of transforming growth factor-beta 1 mRNA and protein in mouse skin carcinogenesis. Molecular carcinogenesis 1994, 9(4):220-229. 10.1002/mc.2940090406, 8148055.
57. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996, 271(5247):350-353. 10.1126/science.271.5247.350, 8553070.
58. Zhang Y, Feng X, We R, Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature 1996, 383(6596):168-172. 10.1038/383168a0, 8774881.
59. Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, Willson JK, Markowitz S, Hamilton SR, Kern SE, et al. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nature genetics 1996, 13(3):343-346. 10.1038/ng0796-343, 8673134.
60. Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 1998, 280(5366):1086-1088. 10.1126/science.280.5366.1086, 9582123.
61. Miyaki M, Kuroki T. Role of Smad4 (DPC4) inactivation in human cancer. Biochemical and biophysical research communications 2003, 306(4):799-804. 10.1016/S0006-291X(03)01066-0, 12821112.
62. Yang G, Yang X. Smad4-mediated TGF-beta signaling in tumorigenesis. International journal of biological sciences 2010, 6(1):1-8. 2808050, 20087440.
63. Bornstein S, White R, Malkoski S, Oka M, Han G, Cleaver T, Reh D, Andersen P, Gross N, Olson S, et al. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation. The Journal of clinical investigation 2009, 119(11):3408-3419. 2769185, 19841536.
64. Kim SK, Fan Y, Papadimitrakopoulou V, Clayman G, Hittelman WN, Hong WK, Lotan R, Mao L. DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer research 1996, 56(11):2519-2521.
65. Fukuchi M, Masuda N, Miyazaki T, Nakajima M, Osawa H, Kato H, Kuwano H. Decreased Smad4 expression in the transforming growth factor-beta signaling pathway during progression of esophageal squamous cell carcinoma. Cancer 2002, 95(4):737-743. 10.1002/cncr.10727, 12209716.
66. Natsugoe S, Xiangming C, Matsumoto M, Okumura H, Nakashima S, Sakita H, Ishigami S, Baba M, Takao S, Aikou T. Smad4 and transforming growth factor beta1 expression in patients with squamous cell carcinoma of the esophagus. Clinical cancer research: an official journal of the American Association for Cancer Research 2002, 8(6):1838-1842.
67. Wang X, Sun W, Bai J, Ma L, Yu Y, Geng J, Qi J, Shi Z, Fu S. Growth inhibition induced by transforming growth factor-beta1 in human oral squamous cell carcinoma. Molecular biology reports 2009, 36(5):861-869. 10.1007/s11033-008-9256-x, 18418730.
68. Sirard C, de la Pompa JL, Elia A, Itie A, Mirtsos C, Cheung A, Hahn S, Wakeham A, Schwartz L, Kern SE, et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 1998, 12(1):107-119. 10.1101/gad.12.1.107, 316400, 9420335.
69. Yang X, Li C, Xu X, Deng C. The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proc Natl Acad Sci USA 1998, 95(7):3667-3672. 10.1073/pnas.95.7.3667, 19893, 9520423.
70. Yang L, Mao C, Teng Y, Li W, Zhang J, Cheng X, Li X, Han X, Xia Z, Deng H, et al. Targeted disruption of Smad4 in mouse epidermis results in failure of hair follicle cycling and formation of skin tumors. Cancer research 2005, 65(19):8671-8678. 10.1158/0008-5472.CAN-05-0800, 16204035.
71. Qiao W, Li AG, Owens P, Xu X, Wang XJ, Deng CX. Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin. Oncogene 2006, 25(2):207-217.
72. Teng Y, Sun AN, Pan XC, Yang G, Yang LL, Wang MR, Yang X. Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse. Cancer research 2006, 66(14):6972-6981. 10.1158/0008-5472.CAN-06-0507, 16849541.
73. Li W, Qiao W, Chen L, Xu X, Yang X, Li D, Li C, Brodie SG, Meguid MM, Hennighausen L, et al. Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in Smad4/Dpc4 conditional knockout mice. Development 2003, 130(24):6143-6153. 10.1242/dev.00820, 14597578.
74. Kutler DI, Auerbach AD, Satagopan J, Giampietro PF, Batish SD, Huvos AG, Goberdhan A, Shah JP, Singh B. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Archives of otolaryngology--head & neck surgery 2003, 129(1):106-112. 10.1001/archotol.129.1.106, 21822898.
75. Owens P, Engelking E, Han G, Haeger SM, Wang XJ. Epidermal Smad4 deletion results in aberrant wound healing. AmJPathol 2010, 176(1):122-133.
76. Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, Hezel AF, Horner J, Lauwers GY, Hanahan D, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes & development 2006, 20(22):3130-3146. 10.1101/gad.1478706, 3251308, 22229114.