Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes

EMBO Molecular Medicine

Volumn 5, Issue 11, 2013, Pages 1720-1739

  Yoon, Jeong Hwan ^a,b,c,d   Jung, Su Myung ^e   Park, Seok Hee ^e   Kato, Mitsuyasu ^a   Yamashita, Tadashi ^b,f   Lee, In Kyu ^b   Sudo, Katsuko ^c   Nakae, Susumu ^g   Han, Jin Soo ^h   Kim, Ok Hee ⁱ   Oh, Byung Chul ⁱ   Sumida, Takayuki ^a   Kuroda, Masahiko ^c   Ju, Ji Hyeon ^j   Jung, Kyeong Cheon ^k   Park, Seong Hoe ^k   Kim, Dae Kee ^l   Mamura, Mizuko ^c,d,m  

^a UNIVERSITY OF TSUKUBA   (Japan)

^b Kyungpook National University School of Medicine   (South Korea)

^c TOKYO MEDICAL UNIVERSITY   (Japan)

^d CHA University   (South Korea)

^e Sungkyunkwan University   (South Korea)

^f AZABU UNIVERSITY   (Japan)

^g UNIVERSITY OF TOKYO   (Japan)

^h Konkuk University   (South Korea)

ⁱ Gachon University College of Medicine   (South Korea)

^j The Catholic University of Korea   (South Korea)

^k Seoul National University   (South Korea)

^l Ewha Womans University   (South Korea)

^m Bundang CHA Hospital   (South Korea)

more..

Author keywords

ALK5 inhibitor; Eomes; Melanoma; Smad4; TGF

Indexed keywords

ANTINEOPLASTIC AGENT; EOMESODERMIN; EW 7197; GALUNISERTIB; RECEPTOR REGULATED SMAD PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; T BOX TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; UBIQUITIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CYTOTOXIC T LYMPHOCYTE; DOWN REGULATION; DRUG MECHANISM; ENZYME INHIBITION; MELANOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION;

ALK5 INHIBITOR; EOMES; MELANOMA; SMAD4; TGF-Β;

ANIMALS; FEMALE; HUMANS; MALE; MELANOMA; MICE; MICE, INBRED C57BL; PROTEIN-SERINE-THREONINE KINASES; PROTEOLYSIS; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; SMAD4 PROTEIN; T-BOX DOMAIN PROTEINS; T-LYMPHOCYTES, CYTOTOXIC; UBIQUITIN; UBIQUITINATION; UP-REGULATION;

EID: 84887041662     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201302524     Document Type: Article

References (62)

1. Akhurst RJ, Hata A (2012) Targeting the TGFbeta signalling pathway in disease. Nat Rev Drug Discov 11: 790-811
2. Bierie B, Moses HL (2006) Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6: 506-520
3. Brown KA, Pietenpol JA, Moses HL (2007) A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem 101: 9-33
4. Callahan JF, Burgess JL, Fornwald JA, Gaster LM, Harling JD, Harrington FP, Heer J, Kwon C, Lehr R, Mathur A, et al (2002) Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5). J Med Chem 45: 999-1001
5. Calvo-Aller E, Baselga J, Glatt S, Cleverly A, Lahn M, Arteaga CL, Rothenberg ML, Carducci MA (2008) First human dose escalation study in patients with metastatic malignancies to determine safety and pharmacokinetics of LY2157299, a small molecule inhibitor of the transforming growth factor-β receptor I kinase. J Clin Oncol 26 (abstr 14554)
6. Chang X, Liu F, Wang X, Lin A, Zhao H, Su B (2011) The kinases MEKK2 and MEKK3 regulate transforming growth factor-β-mediated helper T cell differentiation. Immunity 34: 201-212
7. Cho HI, Lee YR, Celis E (2011) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood 117: 135-144
8. Cruz-Guilloty F, Pipkin ME, Djuretic IM, Levanon D, Lotem J, Lichtenheld MG, Groner Y, Rao A (2009) Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med 206: 51-59
9. De Boeck M, ten Dijke P (2012) Key role for ubiquitin protein modification in TGFbeta signal transduction. Ups J Med Sci 117: 153-165
10. Donkor MK, Sarkar A, Savage PA, Franklin RA, Johnson LK, Jungbluth AA, Allison JP, Li MO (2011) T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-beta1 cytokine. Immunity 35: 123-134
11. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P (2010) The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 10: 554-567
12. Glimcher LH, Townsend MJ, Sullivan BM, Lord GM (2004) Recent developments in the transcriptional regulation of cytolytic effector cells. Nat Rev Immunol 4: 900-911
13. Gorelik L, Flavell RA (2001) Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 7: 1118-1122
14. Gu AD, Wang Y, Lin L, Zhang SS, Wan YY (2012) Requirements of transcription factor Smad-dependent and -independent TGF-beta signaling to control discrete T-cell functions. Proc Natl Acad Sci USA 109: 905-910
15. Hahn JN, Falck VG, Jirik FR (2011) Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in mice. J Clin Invest 121: 4030-4042
16. Hawinkels LJ, ten Dijke P (2011) Exploring anti-TGF-beta therapies in cancer and fibrosis. Growth Factors 29: 140-152
17. Heldin CH, Moustakas A (2012) Role of Smads in TGFβ signaling. Cell Tissue Res 347: 21-36
18. Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, et al (2011) Transcription factor Smad-independent T helper 17 cell induction by transforming-growth factor-beta is mediated by suppression of eomesodermin. Immunity 34: 741-754
19. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, Palanivel VR, Mullen AC, Gasink CR, Kaech SM, Miller JD, et al (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6: 1236-1244
20. Izzi L, Attisano L (2004) Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23: 2071-2078
21. Javelaud D, Alexaki VI, Mauviel A (2008) Transforming growth factor-beta in cutaneous melanoma. Pigment Cell Melanoma Res 21: 123-132
22. Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Mohan AV, et al (2011) Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1, 2, 4]triazolo[1, 5-a]pyridin-6-yl)pyra zoles as transforming growth factor-beta type 1 receptor kinase inhibitors. Bioorg Med Chem Lett 21: 6049-6053
23. Karlsson G, Blank U, Moody JL, Ehinger M, Singbrant S, Deng CX, Karlsson S (2007) Smad4 is critical for self-renewal of hematopoietic stem cells. J Exp Med 204: 467-474
24. Kim BG, Li C, Qiao W, Mamura M, Kasprzak B, Anver M, Wolfraim L, Hong S, Mushinski E, Potter M, et al (2006) Smad4 signalling in T cells is required for suppression of gastrointestinal cancer. Nature 441: 1015-1019
25. Kim DK, Sheen YY, Jin CH, Park CY, Sreenu D, Rao KS, et al (2011) Method of treating fibrosis, cancer and vascular injuries. U.S. Pat. Appl. Publ. US 2011/0319408 A1, p. 8
26. Kirkwood JM, Tarhini AA, Panelli MC, Moschos SJ, Zarour HM, Butterfield LH, Gogas HJ (2008) Next generation of immunotherapy for melanoma. J Clin Oncol 26: 3445-3455
27. Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, Perez-Melgosa M, Sweetser MT, Schlissel MS, Nguyen S, et al (2001) A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15: 763-774
28. Lee YS, Park JS, Kim JH, Jung SM, Lee JY, Kim SJ, Park SH (2011) Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling. Nat Commun 2: 460
29. Li L, Xin H, Xu X, Huang M, Zhang X, Chen Y, Zhang S, Fu XY, Chang Z (2004) CHIP mediates degradation of Smad proteins and potentially regulates Smad-induced transcription. Mol Cell Biol 24: 856-864
30. Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006) Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24: 99-146
31. Liu Y, Festing MH, Hester M, Thompson JC, Weinstein M (2004) Generation of novel conditional and hypomorphic alleles of the Smad2 gene. Genesis 40: 118-123
32. Luo J, Ho PP, Buckwalter MS, Hsu T, Lee LY, Zhang H, Kim DK, Kim SJ, Gambhir SS, Steinman L, et al (2007) Glia-dependent TGF-beta signaling, acting independently of the TH17 pathway, is critical for initiation of murine autoimmune encephalomyelitis. J Clin Invest 117: 3306-3315
33. Martinez GJ, Zhang Z, Chung Y, Reynolds JM, Lin X, Jetten AM, Feng XH, Dong C (2009) Smad3 differentially regulates the induction of regulatory and inflammatory T cell differentiation. J Biol Chem 284: 35283-35286
34. Martinez GJ, Zhang Z, Reynolds JM, Tanaka S, Chung Y, Liu T, Robertson E, Lin X, Feng XH, Dong C (2010) Smad2 positively regulates the generation of Th17 cells. J Biol Chem 285: 29039-29043
35. Massague J, Seoane J, Wotton D (2005) Smad transcription factors. Genes Dev 19: 2783-2810
36. Matsuzaki K (2013) Smad phospho-isoforms direct context-dependent TGF-β signaling. Cytokine Growth Factor Rev 4: 385-399
37. Mohammad KS, Javelaud D, Fournier PG, Niewolna M, McKenna CR, Peng XH, Duong V, Dunn LK, Mauviel A, Guise TA (2011) TGF-beta-RI kinase inhibitor SD-208 reduces the development and progression of melanoma bone metastases. Cancer Res 71: 175-184
38. Moren A, Imamura T, Miyazono K, Heldin CH, Moustakas A (2005) Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem 280: 22115-22123
39. Nam JS, Terabe M, Mamura M, Kang MJ, Chae H, Stuelten C, Kohn E, Tang B, Sabzevari H, Anver MR, et al (2008) An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Res 68: 3835-3843
40. Narayanan S, Silva R, Peruzzi G, Alvarez Y, Simhadri VR, Debell K, Coligan JE, Borrego F (2010) Human Th1 cells that express CD300a are polyfunctional and after stimulation up-regulate the T-box transcription factor eomesodermin. PLoS ONE 5: e10636
41. Pardali E, Xie XQ, Tsapogas P, Itoh S, Arvanitidis K, Heldin CH, ten Dijke P, Grundström T, Sideras P (2000) Smad and AML proteins synergistically confer transforming growth factor beta1 responsiveness to human germ-line IgA genes. J Biol Chem 275: 3552-3560
42. Paolino M, Penninger JM (2009) E3 ubiquitin ligases in T-cell tolerance. Eur J Immunol 39: 2337-2344
43. Park IK, Letterio JJ, Gorham JD (2007) TGF-beta 1 inhibition of IFN-gamma-induced signaling and Th1 gene expression in CD4+ T cells is Smad3 independent but MAP kinase dependent. Mol Immunol 44: 3283-3290
44. Pearce EL, Mullen AC, Martins GA, Krawczyk CM, Hutchins AS, Zediak VP, Banica M, DiCioccio CB, Gross DA, Mao CA, et al (2003) Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 302: 1041-1043
45. Pedroza-Gonzalez A, Xu K, Wu TC, Aspord C, Tindle S, Marches F, Gallegos M, Burton EC, Savino D, Hori T, et al (2011) Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med 208: 479-490
46. Pellegrini M, Calzascia T, Elford AR, Shahinian A, Lin AE, Dissanayake D, Dhanji S, Nguyen LT, Gronski MA, Morre M, et al (2009) Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med 15: 528-536
47. Peng SL, Townsend MJ, Hecht JL, White IA, Glimcher LH (2004) T-bet regulates metastasis rate in a murine model of primary prostate cancer. Cancer Res 64: 452-455
48. Russell JH, Ley TJ (2002) Lymphocyte-mediated cytotoxicity. Annu Rev Immunol 20: 323-370
49. Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, Ichiyama K, Takahashi R, Asakawa M, Muto G, et al (2010) Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J Immunol 185: 842-855
50. Thomas DA, Massague J (2005) TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8: 369-380
51. Thomson TM, Real FX, Murakami S, Cordon-Cardo C, Old LJ, Houghton AN (1988) Differentiation antigens of melanocytes and melanoma: analysis of melanosome and cell surface markers of human pigmented cells with monoclonal antibodies. J Invest Dermatol 90: 459-466
52. Tinoco R, Alcalde V, Yang Y, Sauer K, Zuniga EI (2009) Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity 31: 145-157
53. Wan M, Cao X, Wu Y, Bai S, Wu L, Shi X, Wang N (2002) Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. EMBO Rep 3: 171-176
54. Wan M, Tang Y, Tytler EM, Lu C, Jin B, Vickers SM, Yang L, Shi X, Cao X (2004) Smad4 protein stability is regulated by ubiquitin ligase SCF beta-TrCP1. J Biol Chem 279: 14484-14487
55. Watkins SK, Zhu Z, Watkins KE, Hurwitz AA (2012) Isolation of immune cells from primary tumors. J Vis Exp 64: e3952
56. Yang X, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C (1999) Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J 18: 1280-1291
57. Yang YA, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, Patel SC, Khozin S, Liu ZY, Green J, et al (2002) Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest 109: 1607-1615
58. Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, et al (2011) Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature 469: 548-553
59. Zhang Y, Derynck R (2000) Transcriptional regulation of the transforming growth factor-beta-inducible mouse germ line Ig alpha constant region gene by functional cooperation of Smad, CREB, and AML family members. J Biol Chem 275: 16979-16985
60. Zhang Y, Feng XH, Derynck R (1998) Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription. Nature 394: 909-913
61. Zhang Q, Yang X, Pins M, Javonovic B, Kuzel T, Kim SJ, Parijs LV, Greenberg NM, Liu V, Guo Y, et al (2005) Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer. Cancer Res 65: 1761-1769
62. Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B (2010) T-bet and eomesodermin are required for T cell-mediated antitumor immune responses. J Immunol 185: 3174-3183