Smad phospho-isoforms direct context-dependent TGF-β signaling

Cytokine and Growth Factor Reviews

Volumn 24, Issue 4, 2013, Pages 385-399

  Matsuzaki, Koichi ^a  

^a KANSAI MEDICAL UNIVERSITY   (Japan)

Author keywords

Carcinogenesis; Cellular signaling; Epithelial mesenchymal transition and cancer; Smad linker phosphorylation; Stem cell

Indexed keywords

CYCLIN DEPENDENT KINASE; PROTEIN KINASE; SMAD PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; UBIQUITIN PROTEIN LIGASE E3;

CANCER RISK; CHRONIC LIVER DISEASE; COLON CARCINOGENESIS; ENZYME ACTIVITY; HUMAN; LIVER CELL CARCINOMA; LIVER FIBROSIS; NONHUMAN; ONCOGENE K RAS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DEPHOSPHORYLATION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION;

CARCINOGENESIS; CELLULAR SIGNALING; EPITHELIAL-MESENCHYMAL TRANSITION AND CANCER; SMAD LINKER PHOSPHORYLATION; STEM CELL;

ANIMALS; CELL DIFFERENTIATION; CELL TRANSFORMATION, NEOPLASTIC; EPITHELIAL CELLS; HUMANS; MICE; NEOPLASMS; PHOSPHORYLATION; PROTEIN ISOFORMS; PROTEIN KINASES; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD PROTEINS; TRANSFORMING GROWTH FACTOR BETA;

EID: 84883811151     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2013.06.002     Document Type: Review

References (150)

1. Roberts A.B., Sporn M.B. The transforming growth factor-βs. Peptide growth factors and their receptors 1990, 419-472. Springer, Berlin. M.B. Sporn, A.B. Roberts (Eds.).
2. Wakefield L.M., Roberts A.B. TGF-β signaling: positive and negative effects on tumorigenesis. Current Opinion in Genetics and Development 2002, 12:22-29.
3. Bierie B., Moses H.L. Tumour microenvironment: TGF-β: the molecular Jekyll and Hyde of cancer. Nature Reviews Cancer 2006, 6:506-520.
4. Heldin C.H., Moustakas A. Role of Smads in TGF-β signaling. Cell and Tissue Research 2012, 347:21-36.
5. Moses H.L., Serra R. Regulation of differentiation by TGF-β. Current Opinion in Genetics and Development 1996, 6:581-586.
6. Oft M., Peli J., Rudaz C., Schwarz H., Beug H., Reichmann E. TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes and Development 1996, 10:2462-2477.
7. Watabe T., Miyazono K. Roles of TGF-β family signaling in stem cell renewal and differentiation. Cell Research 2009, 19:103-115.
8. Massagué J. TGF-β signalling in context. Nature Reviews Molecular Cell Biology 2012, 13:616-630.
9. Heldin C.H., Miyazono K., ten Dijke P. TGF-β signaling from cell membrane to nucleus through SMAD proteins. Nature 1997, 390:465-471.
10. Derynck R., Miyazono K. The TGF-β family 2008, Cold Spring Harbor Laboratory Press, NY.
11. Guo X., Wang X.-F. Signaling cross-talk between TGF-β/BMP and other pathways. Cell Research 2009, 19:71-88.
12. Wrana J.L. Regulation of Smad activity. Cell 2000, 100:189-192.
13. Derynck R., Zhang Y., Feng X.-H. Smads: transcriptional activators of TGF-β responses. Cell 1998, 95:737-740.
14. Kretzschmar M., Doody J., Timokhina I., Massagué J. A mechanism of repression of TGF-β/Smad signaling by oncogenic Ras. Genes and Development 1999, 13:804-816.
15. Liu F. Smad3 phosphorylation by cyclin-dependent kinases. Cytokine and Growth Factor Reviews 2006, 17:9-17.
16. Wrighton K.H., Lin X., Feng X.-H. Phospho-control of TGF-β superfamily signaling. Cell Research 2009, 19:8-20.
17. Matsuzaki K. Smad phosphoisoform signaling specificity: the right place at the right time. Carcinogenesis 2011, 32:1578-1588.
18. Hill C.S. Nucleocytoplasmic shuttling of Smad proteins. Cell Research 2009, 19:36-46.
19. Inoue Y., Imamura T. Regulation of TGF-β family signaling by E3 ubiquitin ligases. Cancer Science 2008, 99:2107-2112.
20. Millet C., Yamashita M., Heller M., Yu L.R., Veenstra T.D., Zhang Y.E. A negative feedback control of transforming growth factor-β signaling by glycogen synthase kinase 3-mediated Smad3 linker phosphorylation at Ser-204. Journal of Biological Chemistry 2009, 284:19808-19816.
21. Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F. Cyclin-dependent kinases regulate the antiproliferative function of Smads. Nature 2004, 430:226-231.
22. Sekimoto G., Matsuzaki K., Yoshida K., Mori S., Murata M., Seki T., et al. Reversible Smad-dependent signaling between tumor suppression and oncogenesis. Cancer Research 2007, 67:5090-5096.
23. Matsuzaki K., Kitano C., Murata M., Sekimoto G., Yoshida K., Uemura Y., et al. Smad2 and Smad3 phosphorylated at both linker and COOH-terminal regions transmit malignant TGF-β signal in later stages of human colorectal cancer. Cancer Research 2009, 69:5321-5330.
24. Alarcón C., Zaromytidou A.I., Xi Q., Gao S., Yu J., Fujisawa S., et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-β pathways. Cell 2009, 139:757-769.
25. Mori S., Matsuzaki K., Yoshida K., Furukawa F., Tahashi Y., Yamagata H., et al. TGF-β and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions. Oncogene 2004, 23:7416-7429.
26. Wang G., Matsuura I., He D., Liu F. Transforming growth factor-β-inducible phosphorylation of Smad3. Journal of Biological Chemistry 2009, 284:9663-9673.
27. Matsuzaki K., Murata M., Yoshida K., Sekimoto G., Uemura Y., Sakaida N., et al. Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor β signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 2007, 46:48-57.
28. Gao S., Alarcón C., Sapkota G., Rahman S., Chen P.Y., Goerner N., et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-β signaling. Molecular Cell 2009, 36:457-468.
29. Yumoto K., Thomas P.S., Lane J., Matsuzaki K., Inagaki M., Ninomiya-Tsuji J., et al. TGF-β-activated kinase 1 (Tak1) mediates agonist-induced Smad activation and linker region phosphorylation in embryonic craniofacial neural crest-derived cells. Journal of Biological Chemistry 2013, 288:13467-13480.
30. Matsuura I., Wang G., He D., Liu F. Identification and characterization of ERK MAP kinase phosphorylation sites in Smad3. Biochemistry 2005, 44:12546-12553.
31. van der Velden J.L., Alarcón J.F., Guala A.S., Badura E.C., Janssen-Heininger Y.M. c-Jun N-Terminal Kinase 1 promotes TGF-β1-induced epithelial to mesenchymal transition via control of linker phosphorylation and transcriptional activity of Smad3. American Journal of Respiratory Cell and Molecular Biology 2011, 44:571-581.
32. Furukawa F., Matsuzaki K., Mori S., Tahashi Y., Yoshida K., Sugano Y., et al. p38 MAPK mediates fibrogenic signal through Smad3 phosphorylation in rat myofibroblasts. Hepatology 2003, 38:879-889.
33. Kamaraju A.K., Roberts A.B. Role of Rho/ROCK and p38 map kinase pathways in transforming growth factor β mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. Journal of Biological Chemistry 2005, 280:1024-1036.
34. Saito A., Suzuki H.I., Horie M., Ohshima M., Morishita Y., Abiko Y., et al. An integrated expression profiling reveals target genes of TGF-β and TNF-α possibly mediated by micro RNAs in lung cancer cells. PLoS ONE 2013, 8:e56587.
35. Guo X., Ramirez A., Waddell D.S., Li Z., Liu X., Wang X.F. Axin and GSK3-β control Smad3 protein stability and modulate TGF-β signaling. Genes and Development 2008, 22:106-120.
36. Abushahba W., Olabisi O.O., Jeong B.S., Boregowda R.K., Wen Y., Liu F., et al. Non-canonical Smads phosphorylation induced by the glutamate release inhibitor, riluzole, through GSK3 activation in melanoma. PLoS ONE 2012, 7:e47312.
37. Tang L.Y., Yamashita M., Coussens N.P., Tang Y., Wang X., Li C., et al. Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3. EMBO Journal 2011, 30:4777-4789.
38. Piek E., Heldin C.H., Ten Dijke P. Specificity, diversity, and regulation in TGF-β superfamily signaling. FASEB Journal 1999, 13:2105-2124.
39. Brown K.A., Pietenpol J.A., Moses H.L. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-β signaling. Journal of Cellular Biochemistry 2007, 101:9-33.
40. Matsuzaki K. Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells. Cell and Tissue Research 2012, 347:225-243.
41. Rich J.N., Zhang M., Datto M.B., Bigner D.D., Wang X.-F. Transforming growth factor-β-mediated p15(INK4B) induction and growth inhibition in astrocytes is SMAD3-dependent and a pathway prominently altered in human glioma cell lines. Journal of Biological Chemistry 1999, 274:35053-35058.
42. Ashcroft G.S., Yang X., Glick A.B., Weinstein M., Letterio J.L., Mizel D.E., et al. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nature Cell Biology 1999, 1:260-266.
43. Kretschmer A., Moepert K., Dames S., Sternberger M., Kaufmann J., Klippel A. Differential regulation of TGF-β signaling through Smad2, Smad3 and Smad4. Oncogene 2003, 22:6748-6763.
44. Ink4B transcription in response to TGF-β. EMBO Journal 2000, 19:5178-5193.
45. Pardali K., Kurisaki A., Morén A., ten Dijke P., Kardassis D., Moustakas A. Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-β. Journal of Biological Chemistry 2000, 275:29244-29256.
46. Frederick J.P., Liberati N.T., Waddell D.S., Shi Y., Wang X.-F. Transforming growth factor β-mediated transcriptional repression of c-myc is dependent on direct binding of Smad3 to a novel repressive Smad binding element. Molecular and Cellular Biology 2004, 24:2546-2559.
47. Yagi K., Furuhashi M., Aoki H., Goto D., Kuwano H., Sugamura K., et al. c-myc is a downstream target of the Smad pathway. Journal of Biological Chemistry 2002, 277:854-861.
48. Yang Y.A., Zhang G.M., Feigenbaum L., Zhang Y.E. Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer Cell 2006, 9:445-457.
49. Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., et al. PPM1A functions as a Smad phosphatase to terminate TGFβ signaling. Cell 2006, 125:915-928.
50. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell 2000, 103:239-252.
51. Wagner E.F., Nebrada A.R. Signal integration by JNK and p38 MAPK pathways in cancer development. Nature Reviews Cancer 2009, 9:537-549.
52. Engel M.E., McDonnell M.A., Law B.K., Moses H.L. Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription. Journal of Biological Chemistry 1999, 274:37413-37420.
53. Wang G., Long J., Matsuura I., He D., Liu F. The Smad3 linker region contains a transcriptional activation domain. Biochemical Journal 2005, 386:29-34.
54. Prokova V., Mavridou S., Papakosta P., Kardassis D. Characterization of a novel transcriptionally active domain in the transforming growth factor β-regulated Smad3 protein. Nucleic Acids Research 2005, 33:3708-3721.
55. Alarcón J.F., Guala A.S., van der Velden J., McElhinney B., Irvin C.G., Davis R.J., et al. Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-β1. Journal of Cell Science 2008, 121:1036-1045.
56. Liu F., Pouponnot C., Massagué J. Dual role of the Smad4/DPC4 tumor suppressor in TGF-β-inducible transcriptional complexes. Genes and Development 1997, 11:3157-3167.
57. Yamagata H., Matsuzaki K., Mori S., Yoshida K., Tahashi Y., Furukawa F., et al. Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis. Cancer Research 2005, 65:157-165.
58. Yoshida K., Matsuzaki K., Mori S., Tahashi Y., Yamagata H., Furukawa F., et al. Transforming growth factor-β and platelet-derived growth factor signal via c-Jun N-terminal kinase-dependent Smad2/3 phosphorylation in rat hepatic stellate cells after acute liver injury. American Journal of Pathology 2005, 166:1029-1039.
59. Murata M., Matsuzaki K., Yoshida K., Sekimoto G., Tahashi Y., Mori S., et al. Hepatitis B virus X protein shifts human hepatic TGF-β signaling from tumor-suppression to oncogenesis in early chronic hepatitis B. Hepatology 2009, 49:1203-1217.
60. Nagata H., Hatano E., Tada M., Murata M., Kitamura K., Asechi H., et al. Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor-suppression in rat hepatocellular carcinoma. Hepatology 2009, 49:1944-1953.
61. Kawamata S., Matsuzaki K., Murata M., Seki T., Matsuoka K., Iwao Y., et al. Oncogenic Smad3 signaling induced by chronic inflammation is an early event in ulcerative colitis-associated carcinogenesis. Inflammatory Bowel Diseases 2011, 17:683-695.
62. Yamaguchi T., Matsuzaki K., Inokuchi R., Kawamura R., Yoshida K., Murata M., et al. Phosphorylated Smad2 and Smad3 signaling: Shifting between tumor suppression and fibro-carcinogenesis in chronic hepatitis C. Hepatology Research 2013, [Epub ahead of print].
63. Feng X.-H., Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annual Review of Cell and Developmental Biology 2005, 21:659-693.
64. Kang Y., He W., Tulley S., Gupta G.P., Serganova I., Chen C.R., et al. Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proceedings of the National Academy of Sciences of the United States of America 2005, 102:13909-13914.
65. Marshall C.J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal regulated kinase activation. Cell 1995, 80:179-185.
66. Mulcahy L.S., Smith M.R., Stacey D.W. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells. Nature 1985, 313:241-243.
67. Roberts A.B., Tian F., Byfield S.D., Stuelten C., Ooshima A., Saika S., et al. Smad3 is key to TGF-β-mediated epithelial-to-mesenchymal transition, fibrosis, tumor suppression and metastasis. Cytokine and Growth Factor Reviews 2006, 17:19-27.
68. Hamajima H., Ozaki I., Zhang H., Iwane S., Kawaguchi Y., Eguchi Y., et al. Modulation of the transforming growth factor-β1-induced Smad phosphorylation by the extracellular matrix receptor β1-integrin. International Journal of Oncology 2009, 35:1441-1447.
69. Chen D., Lin Q., Box N., Roop D., Ishii S., Matsuzaki K., et al. SKI knockdown inhibits human melanoma tumor growth in vivo. Pigment Cell & Melanoma Research 2009, 22:761-772.
70. Hui L., Zatloukal K., Scheuch H., Stepniak E., Wagner E.F. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. Journal of Clinical Investigation 2008, 118:3943-3953.
71. Arany P.R., Rane S.G., Roberts A.B. Smad3 deficiency inhibits v-ras-induced transformation by suppression of JNK MAPK signaling and increased farnesyl transferase inhibition. Oncogene 2008, 27:2507-2512.
72. Moustakas A., Pardali K., Gaal A., Heldin C.H. Mechanisms of TGF-β signaling in regulation of cell growth and differentiation. Immunology Letters 2002, 82:85-91.
73. Mu X., Lin S., Yang J., Chen C., Chen Y., Herzig M.C., et al. TGF-β signaling is often attenuated during hepatotumorigenesis, but is retained for the malignancy of hepatocellular carcinoma cells. PLoS ONE 2013, 8:e63436.
74. Glick A.B., Weinberg W.C., Wu I.H., Quan W., Yuspa S.H. Transforming growth factor β1 suppresses genomic instability independent of a G1 arrest, p53, and Rb. Cancer Research 1996, 56:3645-3650.
75. Tremain R., Marko M., Kinnimulki V., Ueno H., Bottinger E., Glick A. Defects in TGF-β signaling overcome senescence of mouse keratinocytes expressing v-Ha-ras. Oncogene 2000, 19:1698-1709.
76. Wrighton K.H., Willis D., Long J., Liu F., Lin X., Feng X.-H. Small C-terminal domain phosphatases dephosphorylate the regulatory linker regions of Smad2 and Smad3 to enhance transforming growth factor-β signaling. Journal of Biological Chemistry 2006, 281:38365-38375.
77. Sapkota G., Knockaert M., Alarcón C., Montalvo E., Brivanlou A.H., Massagué J. Dephosphorylation of the linker regions of Smad1 and Smad2/3 by small C-terminal domain phosphatases has distinct outcomes for bone morphogenetic protein and transforming growth factor-β pathways. Journal of Biological Chemistry 2006, 281:40412-40419.
78. Brown J.D., DiChiara M.R., Anderson K.R., Gimbrone M.A., Topper J.N. MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells. Journal of Biological Chemistry 1999, 274:8797-8805.
79. de Caestecker M.P., Parks W.T., Frank C.J., Castagnino P., Bottaro D.P., Roberts A.B., et al. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes and Development 1998, 12:1587-1592.
80. Grimm O.H., Gurdon J.B. Nuclear exclusion of Smad2 is a mechanism leading to loss of competence. Nature Cell Biology 2002, 4:519-522.
81. Macias-Silva M., Abdollah S., Hoodless P.A., Pirone R., Attisano L., Wrana J.L. MADR2 is a substrate of the TGF-β receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 1996, 87:1215-1224.
82. Burch M.L., Yang S.N., Ballinger M.L., Getachew R., Osman N., Little P.J. TGF-β stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2. Cellular and Molecular Life Sciences 2010, 67:2077-2090.
83. Shepherd R.D., Kos S.M., Rinker K.D. Flow-dependent Smad2 phosphorylation and TGIF nuclear localization in human aortic endothelial cells. Journal of Physiology: Heart and Circulatory Physiology 2011, 301:98-107.
84. Hough C., Radu M., Dore J.J. TGF-β induced Erk phosphorylation of Smad linker region regulates Smad signaling. PLoS ONE 2012, 7:e42513.
85. Yamaguchi K., Shirakabe K., Shibuya H., Irie K., Oishi I., Ueno N., et al. Identification of a member of the MAPKKK family as a potential mediator of TGF-β signal transduction. Science 1995, 270:2008-2011.
86. Lehmann K., Janda E., Pierreux C.E., Rytmaa M., Schulze A., McMahon M., et al. Raf induces TGF-β production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes and Development 2000, 14:2610-2622.
87. Janda E., Lehmann K., Killisch I., Jechlinger M., Herzig M., Downward J., et al. Ras and TGF-β cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. Journal of Cell Biology 2002, 156:299-313.
88. Freytag J., Wilkins-Port C.E., Higgins C.E., Higgins S.P., Samarakoon R., Higgins P.J. PAI-1 mediates the TGF-β1+EGF-induced "scatter" response in transformed human keratinocytes. Journal of Investigative Dermatology 2010, 130:2179-2190.
89. Bajou K., Noël A., Gerard R.D., Masson V., Brunner N., Holst-Hansen C., et al. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nature Medicine 1998, 4:923-928.
90. Piek E., Ju W.J., Heyer J., Escalante-Alcalde D., Stewart C.L., Weinstein M., et al. Functional characterization of transforming growth factor β signaling in Smad2- and Smad3-deficient fibroblasts. Journal of Biological Chemistry 2001, 276:19945-19953.
91. Zhang Y., Feng X., We R., Derynck R. Receptor-associated Mad homologues synergize as effectors of the TGF-β response. Nature 1996, 383:168-172.
92. Liu X., Sun Y., Constantinescu S.N., Karam E., Weinberg R.A., Lodish H.F. Transforming growth factor β-induced phosphorylation of Smad3 is required for growth inhibition and transcriptional induction in epithelial cells. Proceedings of the National Academy of Sciences of the United States of America 1997, 94:10669-10674.
93. Yang Y.C., Piek E., Zavadil J., Liang D., Xie D., Heyer J., et al. Hierarchical model of gene regulation by transforming growth factor β. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:10269-10274.
94. Kessenbrock K., Plaks V., Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010, 141:52-67.
95. Seong H.A., Jung H., Ha H. Murine protein serine/threonine kinase 38 stimulates TGF-β signaling in a kinase-dependent manner via direct phosphorylation of Smad proteins. Journal of Biological Chemistry 2010, 285:30959-30970.
96. Wu D., Pan W. GSK3: a multifaceted kinase in Wnt signaling. Trends in Biochemical Sciences 2010, 35:161-168.
97. Hayashida T., de Caestecker M., Schnaper H.W. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-β-dependent responses in human mesangial cells. FASEB Journal 2003, 17:1576-1578.
98. Yang Y., Yang S., Chen M., Zhang X., Zou Y., Zhang X. Compound Astragalus and Salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-β/Smad signaling in myofibroblasts. Journal of Ethnopharmacology 2008, 118:264-270.
99. Li F., Zeng B., Chai Y., Cai P., Fan C., Cheng T. The linker region of Smad2 mediates TGF-β-dependent ERK2-induced collagen synthesis. Biochemical and Biophysical Research Communication 2009, 386:289-293.
100. Jiang W., Zhang Y., Wu H., Zhang X., Gan H., Sun J., et al. Role of cross-talk between the Smad2 and MAPK pathways in TGF-β1-induced collagen IV expression in mesangial cells. International Journal of Molecular Medicine 2010, 26:571-576.
101. Jablonska E., Markart P., Zakrzewicz D., Preissner K.T., Wygrecka M. Transforming growth factor-β1 induces expression of human coagulation factor XII via Smad3 and JNK signaling pathways in human lung fibroblasts. Journal of Biological Chemistry 2010, 285:11638-11651.
102. Matsuura I., Chiang K.N., Lai C.Y., He D., Wang G., Ramkumar R., et al. Pin1 promotes transforming growth factor-β-induced migration and invasion. Journal of Biological Chemistry 2010, 285:1754-1764.
103. Aragon E., Goerner N., Zaromytidou A.I., Xi Q., Escobedo A., Massagué J., et al. A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes and Development 2011, 25:1275-1288.
104. Zelivianski S., Cooley A., Kall R., Jeruss J.S. Cyclindependent kinase 4-mediated phosphorylation inhibits Smad3 activity in cyclin D-overexpressing breast cancer cells. Molecular Cancer Research 2010, 8:1375-1387.
105. Sherr C.J. Cancer cell cycles. Science 1996, 274:1672-1677.
106. Fuxe J., Vincent T., Garcia de Herreros A. Transcriptional crosstalk between TGF-β and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle 2010, 9:2363-2374.
107. Hirschhorn T., Barizilay L., Smorodinsky N.I., Ehrlich M. Differential regulation of Smad3 and of the type II transforming growth factor-β receptor in mitosis: implications for signaling. PLoS ONE 2012, 7:e43459.
108. Tarasewicz E., Jeruss J.S. Phospho-specific Smad3 signaling: impact on breast oncogenesis. Cell Cycle 2012, 11:2443-2451.
109. Cooley A., Zelivianski S., Jeruss J.S. Impact of cyclin E overexpression on Smad3 activity in breast cancer cell lines. Cell Cycle 2010, 9:4900-4907.
110. Yeh E.S., Means A.R. PIN1, the cell cycle and cancer. Nature Reviews Cancer 2007, 7:381-388.
111. Nakano A., Koinuma D., Miyazawa K., Uchida T., Saitoh M., Kawabata M., et al. Pin1 down-regulates transforming growth factor-β (TGF-β) signaling by inducing degradation of Smad proteins. Journal of Biological Chemistry 2009, 284:6109-6115.
112. Zhu H., Kavsak P., Abdollah S., Wrana J.L., Thomsen G.H. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 1999, 400:687-693.
113. Lin X., Liang M., Feng X.-H. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-β signaling. Journal of Biological Chemistry 2000, 275:36818-36822.
114. Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K., et al. NEDD4-NEDD2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor. Biochemical Journal 2005, 386:461-470.
115. Izzi L., Attisano L. Regulation of the TGF-β signalling pathway by ubiquitin-mediated degradation. Oncogene 2004, 23:2071-2078.
116. Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., et al. USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nature Cell Biology 2011, 13:1368-1375.
117. Clevers H., Stem Cells: A unifying theory for the crypt. Nature 2013, 495:53-54.
118. Weinberg R.A. The biology of cancer 2007, Garlang Science, NY.
119. Miyoshi H., Ajima R., Luo C.T., Yamaguchi T.P., Stappenbeck T.S. Wnt5α potentiates TGF-β signaling to promote colonic crypt regeneration after tissue injury. Science 2012, 338:108-113.
120. Fukui T., Kishimoto M., Nakajima A., Yamashina M., Nakayama S., Kusuda T., et al. The specific linker phosphorylation of Smad2/3 indicates epithelial stem cells in stomach; particularly increasing in mucosae of Helicobacter-associated gastritis. Journal of Gastroenterology 2011, 46:456-468.
121. Fujishita T., Aoki M., Taketo M.M. JNK signaling promotes intestinal tumorigenesis through activation of mTOR complex 1 in Apc 716 mice. Gastroenterology 2011, 140:1556-1563.
122. Sancho R., Nateri A.S., de Vinuesa A.G., Aguilera C., Nye E., Spencer-Dene B., et al. JNK signaling modulates intestinal homeostasis and tumourigenesis in mice. EMBO Journal 2009, 28:1843-1854.
123. Fearon E.R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990, 61:759-767.
124. Janssen K.P., el-Marjou F., Pinto D., Sastre X., Rouillard D., Fouquet C., et al. Targeted expression of oncogenic K-ras in intestinal epithelium causes spontaneous tumorigenesis in mice. Gastroenterology 2002, 123:492-504.
125. Feng Y., Bommer G.T., Zhao J., Green M., Sands E., Zhai Y., et al. Mutant KRAS promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool. Gastroenterology 2011, 141:1003-1013.
126. Licato L.L., Brenner D.A. Analysis of signaling protein kinases in human colon or colorectal carcinomas. Digestive Diseases and Sciences 1998, 43:1454-1464.
127. Licato L.L., Keku T.O., Wurzelmann J.I., Murray S.C., Woosley J.T., Sandler R.S., et al. In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia. Gastroenterology 1997, 113:1589-1598.
128. Javelaud D., Mauviel A. Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-β: implications for carcinogenesis. Oncogene 2005, 24:5742-5750.
129. Cohen-Solal K.A., Merrigan K.T., Chan J.L., Goydos J.S., Chen W., Foran D.J., et al. Constitutive Smad linker phosphorylation in melanoma: a mechanism of resistance to transforming growth factor-β-mediated growth inhibition. Pigment Cell & Melanoma Research 2011, 24:512-524.
130. Cui W., Fowlis D.J., Bryson S., Duffie E., Ireland H., Balmain A., et al. TGF-β1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 1996, 86:531-542.
131. Alcorn J.F., Guala A.S., van der Velden J., McElhinney B., Irvin C.G., Davis R.J., et al. Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-β1. Journal of Cell Science 2008, 121:1036-1045.
132. Wulf G.M., Ryo A., Wulf G.G., Lee S.W., Niu T., Petkova V., et al. Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO Journal 2001, 20:3459-3472.
133. Fukuchi M., Fukai Y., Masuda N., Miyazaki T., Nakajima M., Sohda M., et al. High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Research 2002, 62:7162-7165.
134. Daly A.C., Vizán P., Hill C.S. Smad3 protein levels are modulated by Ras activity and during the cell cycle to dictate transforming growth factor-β responses. Journal of Biological Chemistry 2010, 285:6489-6497.
135. Grünert S., Jechlinger M., Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nature Reviews Molecular Cell Biology 2003, 4:657-665.
136. Oft M., Akhurst R.J., Balmain A. Metastasis is driven by sequential elevation of H-ras and Smad2 levels. Nature Cell Biology 2002, 4:487-494.
137. Mani S.A., Guo W., Liao M.J., Eaton E.N., Ayyanan A., Zhou A.Y., et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
138. Saika S., Kono-Saika S., Ohnishi Y., Sato M., Muragaki Y., Ooshima A., et al. Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. American Journal of Pathology 2004, 164:651-663.
139. Liu Q., Zhang Y., Mao H., Chen W., Luo N., Zhou Q., et al. A crosstalk between the Smad and JNK signaling in the TGF-β-induced epithelial-mesenchymal transition in rat peritoneal mesothelial cells. PLoS ONE 2012, 7:e32009.
140. Bellam N., Pasche B. TGF-β signaling alterations and colon cancer. Cancer Treatment and Research 2010, 155:85-103.
141. Zhang Y.E. Non-Smad pathways in TGF-β signaling. Cell Research 2009, 19:128-139.
142. Moustakas A., Heldin C.H. Non-Smad TGF-β signals. Journal of Cell Science 2005, 118:3573-3584.
143. Ikushima H., Todo T., Ino Y., Takahashi M., Miyazawa K., Miyazono K. Autocrine TGF-β signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors. Cell Stem Cell 2009, 5:504-514.
144. El-Serag H.B., Rudolph K.L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557-2576.
145. Thorgeirsson S.S., Grisham J.W. Molecular pathogenesis of human hepatocellular carcinoma. Nature Genetics 2002, 31:339-346.
146. Friedman S.L. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nature Clinical Practice Gastroenterology & Hepatology 2004, 1:98-105.
147. Kim S.H., Ahn S., Park C.K. Smad3 and its phosphoisoforms are prognostic predictors of hepatocellular carcinoma after curative hepatectomy. Hepatobiliary & Pancreatic Diseases International 2012, 11:51-59.
148. Shiratori Y., Imazeki F., Moriyama M., Yano M., Arakawa Y., Yokosuka O., et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Annals of Internal Medicine 2000, 132:517-524.
149. Yoshida H., Shiratori Y., Moriyama M., Arakawa Y., Ide T., Sata M., et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Annals of Internal Medicine 1999, 131:174-181.
150. Morgan T.R., Ghany M.G., Kim H.Y., Snow K.K., Shiffman M.L., De Santo J.L., et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010, 52:833-844.