Rapamycin inhibits both motility through down-regulation of p-STAT3 (S727) by disrupting the mTORC2 assembly and peritoneal dissemination in sarcomatoid cholangiocarcinoma

Clinical and Experimental Metastasis

Volumn 30, Issue 2, 2013, Pages 177-187

  Hong, Sun Mi ^a   Park, Chang Wook ^a   Cha, Hyung Jin ^a   Kwon, Jung Hee ^a   Yun, Young Sung ^b   Lee, Nam Gyu ^a   Kim, Dae Ghon ^c   Nam, Hong Gil ^a   Choi, Kwan Yong ^a  

^a Pohang University of Science and Technology (POSTECH)   (South Korea)

^b UNIVERSITY OF MINNESOTA   (United States)

^c Chonbuk National University Medical School   (South Korea)

Author keywords

Motility; mTOR pathway; mTORC2 assembly; Peritoneal dissemination; Rapamycin; Sarcomatoid cholangiocarcinoma; STAT3

Indexed keywords

GELATINASE A; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; MESSENGER RNA; PROTEIN KINASE B; RAPAMYCIN; SERINE; STAT3 PROTEIN; TUMOR PROTEIN; TWIST1 PROTEIN; UNCLASSIFIED DRUG; MULTIPROTEIN COMPLEX; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE DUCT CARCINOMA; CANCER CELL CULTURE; CELL DEDIFFERENTIATION; CELL MOTILITY; CHEMOSENSITIVITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; GENE OVEREXPRESSION; MALE; METASTASIS INHIBITION; MOUSE; NONHUMAN; PERITONEUM METASTASIS; PROTEIN ASSEMBLY; PROTEIN PHOSPHORYLATION; SARCOMATOID CARCINOMA; SIGNAL TRANSDUCTION; WILD TYPE; ANIMAL; APOPTOSIS; BILE DUCT TUMOR; CELL ADHESION; CELL MOTION; CELL PROLIFERATION; ENZYME IMMUNOASSAY; GENETICS; HUMAN; IMMUNOPRECIPITATION; INTRAHEPATIC BILE DUCT; METABOLISM; METASTASIS; NUDE MOUSE; PATHOLOGY; PERITONEUM TUMOR; PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BILE DUCT NEOPLASMS; BILE DUCTS, INTRAHEPATIC; BLOTTING, WESTERN; CELL ADHESION; CELL MOVEMENT; CELL PROLIFERATION; CHOLANGIOCARCINOMA; DOWN-REGULATION; HUMANS; IMMUNOENZYME TECHNIQUES; IMMUNOPRECIPITATION; MALE; MICE; MICE, NUDE; MULTIPROTEIN COMPLEXES; PERITONEAL NEOPLASMS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIROLIMUS; STAT3 TRANSCRIPTION FACTOR; TOR SERINE-THREONINE KINASES; TUMOR CELLS, CULTURED;

MLCS; MLOWN;

EID: 84875069539     PISSN: 02620898     EISSN: 15737276     Source Type: Journal    
DOI: 10.1007/s10585-012-9526-9     Document Type: Article

References (34)

1. Patel T, Singh P (2007) Cholangiocarcinoma: emerging approaches to a challenging cancer. Curr Opin Gastroenterol 23(3):317-323
2. Sirica AE (2005) Cholangiocarcinoma: molecular targeting strategies for chemoprevention and therapy. Hepatology 41(1):5-15
3. Nakajima T, Tajima Y, Sugano I, Nagao K, Kondo Y, Wada K (1993) Intrahepatic cholangiocarcinoma with sarcomatous change. Clinicopathologic and immunohistochemical evaluation of seven cases. Cancer 72(6):1872-1877
4. Malhi H, Gores GJ (2006) Cholangiocarcinoma: modern advances in understanding a deadly old disease. J Hepatol 45(6):856-867
5. Efeyan A, Sabatini DM (2010) mTOR and cancer: many loops in one pathway. Curr Opin Cell Biol 22(2):169-176. doi: 10.1016/j.ceb.2009.10.007
6. Dancey J (2010) mTOR signaling and drug development in cancer. Nat Rev Clin Oncol 7(4):209-219. doi: 10.1038/nrclinonc.2010.21
7. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22(2):159-168. doi: 10.4161/cc.10.22.18124
8. Zeng Z, dos Sarbassov D, Samudio IJ, Yee KW, Munsell MF, Ellen Jackson C, Giles FJ, Sabatini DM, Andreeff M, Konopleva M (2007) Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood 109(8):3509-3512
9. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004) Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14(14):1296-1302
10. Wang Z, Zhou J, Fan J, Qiu SJ, Yu Y, Huang XW, Tang ZY (2008) Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 14(16):5124-5130. doi: 10.1158/1078-0432.CCR-07-4774
11. Wang W, Jia WD, Xu GL, Wang ZH, Li JS, Ma JL, Ge YS, Xie SX, Yu JH (2009) Antitumoral activity of rapamycin mediated through inhibition of HIF-1alpha and VEGF in hepatocellular carcinoma. Dig Dis Sci 54(10):2128-2136. doi: 10.1007/s10620-008-0605-3
12. Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T (1994) Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77(1):63-71
13. Darnell JE Jr, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264(5164):1415-1421
14. Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR et al (1995) A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J 14(7):1421-1429
15. Blechacz BR, Gores GJ (2008) Cholangiocarcinoma. Clin Liver Dis 12(1):131-150. doi: 10.1016/j.cld.2007.11.003
16. Wen Z, Zhong Z, Darnell JE Jr (1995) Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82(2):241-250
17. Decker T, Kovarik P (2000) Serine phosphorylation of STATs. Oncogene 19(21):2628-2637. doi: 10.1038/sj.onc.1203481
18. Rajan P, Panchision DM, Newell LF, McKay RD (2003) BMPs signal alternately through a SMAD or FRAP-STAT pathway to regulate fate choice in CNS stem cells. J Cell Biol 161(5):911-921
19. Kim JH, Kim JE, Liu HY, Cao W, Chen J (2008) Regulation of interleukin-6-induced hepatic insulin resistance by mammalian target of rapamycin through the STAT3-SOCS3 pathway. J Biol Chem 283(2):708-715
20. Huang S (2007) Regulation of metastases by signal transducer and activator of transcription 3 signaling pathway: clinical implications. Clin Cancer Res 13(5):1362-1366
21. Cheng GZ, Zhang WZ, Sun M, Wang Q, Coppola D, Mansour M, Xu LM, Costanzo C, Cheng JQ, Wang LH (2008) Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function. J Biol Chem 283(21):14665-14673
22. Yang J, Mani SA, Weinberg RA (2006) Exploring a new twist on tumor metastasis. Cancer Res 66(9):4549-4552
23. Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3(3):207-214. doi: 10.1038/nrm763
24. Kim D-G, Park S-Y, You K-R, Lee G-B, Kim H, Moon W-S, Chun Y-H, Park S-H (2001) Establishment and characterization of chromosomal aberrations in human cholangiocarcinoma cell lines by cross-species color banding. Genes Chromosom Cancer 30(1):48-56
25. Hwang JH, Kim DW, Suh JM, Kim H, Song JH, Hwang ES, Park KC, Chung HK, Kim JM, Lee TH, Yu DY, Shong M (2003) Activation of signal transducer and activator of transcription 3 by oncogenic RET/PTC (rearranged in transformation/papillary thyroid carcinoma) tyrosine kinase: roles in specific gene regulation and cellular transformation. Mol Endocrinol 17(6):1155-1166
26. Lamouille S, Derynck R (2007) Cell size and invasion in TGF-beta induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway. J Cell Biol 178(3):437-451
27. Liu L, Li F, Cardelli JA, Martin KA, Blenis J, Huang S (2006) Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Oncogene 25(53):7029-7040
28. Chung JY, Hong SM, Choi BY, Cho H, Yu E, Hewitt SM (2009) The expression of phospho-AKT, phospho-mTOR, and PTEN in extrahepatic cholangiocarcinoma. Clin Cancer Res 15(2):660-667
29. Nanashima A, Sumida Y, Abo T, Nagasaki T, Takeshita H, Fukuoka H, Sawai T, Tanaka K, Yasutake T, Nagayasu T (2007) Patient outcome and prognostic factors in intrahepatic cholangiocarcinoma after hepatectomy. Hepatogastroenterology 54(80):2337-2342
30. Guertin DA, Sabatini DM (2009) The pharmacology of mTOR inhibition. Sci Signal 2(67):24. doi: 10.1126/scisignal.267pe24
31. Yellen P, Saqcena M, Salloum D, Feng J, Preda A, Xu L, Rodrik-Outmezguine V, Foster DA (2011) High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. Cell Cycle 10(22):3948-3956. doi: 10.4161/cc.10.22.18124
32. Busch S, Renaud SJ, Schleussner E, Graham CH, Markert UR (2009) mTOR mediates human trophoblast invasion through regulation of matrix-remodeling enzymes and is associated with serine phosphorylation of STAT3. Exp Cell Res 315(10):1724-1733
33. Szarvas T, vom Dorp F, Ergun S, Rubben H (2011) Matrix metalloproteinases and their clinical relevance in urinary bladder cancer. Nat Rev Urol 8(5):241-254. doi: 10.1038/nrurol.2011.44
34. Xie TX, Wei D, Liu M, Gao AC, Ali-Osman F, Sawaya R, Huang S (2004) Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 23(20):3550-3560