Aberrant amino acid signaling promotes growth and metastasis of hepatocellular carcinomas through Rab1A-dependent activation of mTORC1 by Rab1A

Oncotarget

Volumn 6, Issue 25, 2015, Pages 20813-20828

  Xu, Bi Hong ^a   Li, Xiao Xing ^a   Yang, Yang ^a   Zhang, Mei Yin ^a   Rao, Hui Lan ^a   Wang, Hui Yun ^a,b   Zheng, X F Steven ^a,b  

^a SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^b ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

Cancer; MTORC1; Rab1A; Rapamcyin; Signal transduction

Indexed keywords

AMINO ACID; GUANOSINE TRIPHOSPHATASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PROTEIN RAB1A; RAPAMYCIN; UNCLASSIFIED DRUG; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; RAB PROTEIN; TARGET OF RAPAMYCIN KINASE; TUMOR MARKER;

ADULT; AMINO ACID SIGNALING; ANIMAL CELL; ARTICLE; CANCER PROGNOSIS; CARCINOGENESIS; CONTROLLED STUDY; DRUG SENSITIVITY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL CARCINOMA; MAJOR CLINICAL STUDY; MALE; METASTASIS; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TUMOR GROWTH; AGED; CELL MOTION; CELL SURVIVAL; CHEMISTRY; COHORT ANALYSIS; GENE DOSAGE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; IMMUNOHISTOCHEMISTRY; LIVER TUMOR; METABOLISM; MIDDLE AGED; PROGNOSIS; TUMOR CELL LINE; TUMOR INVASION; WOUND HEALING;

AGED; AMINO ACIDS; BIOMARKERS, TUMOR; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL MOVEMENT; CELL SURVIVAL; COHORT STUDIES; FEMALE; GENE DOSAGE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOHISTOCHEMISTRY; LIVER NEOPLASMS; MALE; MIDDLE AGED; MULTIPROTEIN COMPLEXES; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; PROGNOSIS; RAB1 GTP-BINDING PROTEINS; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; WOUND HEALING;

EID: 84940749205     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.5175     Document Type: Article

References (36)

1. Siegel R, Naishadham D and Jemal A. Cancer statistics, 2012. CA: a cancer journal for clinicians. 2012; 62:10-29.
2. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011; 61:69-90.
3. Soerjomataram I, Lortet-Tieulent J, Parkin DM, Ferlay J, Mathers C, Forman D and Bray F. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. The Lancet. 2012; 380:1840-1850.
4. Arnaoutakis DJ, Mavros MN, Shen F, Alexandrescu S, Firoozmand A, Popescu I, Weiss M, Wolfgang CL, Choti MA and Pawlik TM. Recurrence patterns and prognostic factors in patients with hepatocellular carcinoma in noncirrhotic liver: a multi-institutional analysis. Annals of surgical oncology. 2014; 21:147-154.
5. Csibi A, Fendt SM, Li C, Poulogiannis G, Choo AY, Chapski DJ, Jeong SM, Dempsey JM, Parkhitko A, Morrison T, Henske EP, Haigis MC, Cantley LC, Stephanopoulos G, Yu J and Blenis J. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell. 2013; 153:840-854.
6. Wullschleger S, Loewith R and Hall M. TOR signaling in growth and metabolism. Cell. 2006; 124:471-484.
7. Laplante M and Sabatini D. mTOR Signaling in Growth Control and Disease. Cell. 2012; 149:274-293.
8. Zhang Y, Duan Y and Zheng X. Targeting the mTOR kinase domain: the second generation of mTOR inhibitors. Drug Discov Today. 2011; 16:325-331.
9. Bjornsti M-A and Houghton PJ. The tor pathway: a target for cancer therapy. Nat Rev Cancer. 2004; 4:335-348.
10. Guertin D and Sabatini D. Defining the role of mTOR in cancer. Cancer Cell. 2007; 12:9-22.
11. Cook KM and Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA: a cancer journal for clinicians. 2010; 60:222-243.
12. Finn RS. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition. Liver Cancer. 2012; 1:247-256.
13. Tsang C, Qi H, Liu L and Zheng X. Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov Today. 2007; 12:112-124.
14. Philip PA, Mahoney MR, Allmer C, Thomas J, Pitot HC, Kim G, Donehower RC, Fitch T, Picus J and Erlichman C. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2005; 23:6657-6663.
15. Stacker SA, Achen MG, Jussila L, Baldwin ME and Alitalo K. Lymphangiogenesis and cancer metastasis. Nature reviews Cancer. 2002; 2:573-583.
16. Galuppo R, Maynard E, Shah M, Daily MF, Chen C, Spear BT and Gedaly R. Synergistic inhibition of HCC and liver cancer stem cell proliferation by targeting RAS/RAF/MAPK and WNT/beta-catenin pathways. Anticancer Res. 2014; 34:1709-1713.
17. Don A and Zheng X. Recent clinical trials of mTOR-targeted cancer therapies. Rev Recent Clin Trials. 2011; 6:24-35.
18. Samuels Y, Diaz LA, Schmidt-Kittler O, Cummins JM, DeLong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 2005; 7:561-573.
19. Beaver JA, Gustin JP, Yi KH, Rajpurohit A, Thomas M, Gilbert SF, Rosen DM, Ho Park B and Lauring J. PIK3CA and AKT1 Mutations Have Distinct Effects on Sensitivity to Targeted Pathway Inhibitors in an Isogenic Luminal Breast Cancer Model System. Clinical Cancer Research. 2013; 19:5413-5422.
20. Chan T-F, Carvalho J, Riles L and Zheng XFS. A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR). PNAS. 2000; 97:13227-13232.
21. Thomas JD, Zhang YJ, Wei YH, Cho JH, Morris LE, Wang HY and Zheng XF. Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer Cell. 2014; 26:754-769.
22. Lamb JR, Zhang C, Xie T, Wang K, Zhang B, Hao K, Chudin E, Fraser HB, Millstein J, Ferguson M, Suver C, Ivanovska I, Scott M, Philippar U, Bansal D, Zhang Z, et al. Predictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting. PLoS One. 2011; 6:e20090.
23. Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clement B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouze E, et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 2012; 44:694-698.
24. Tisdale EJ, Bourne JR, Khosravi-Far R, Der CJ and Balch WE. GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. The Journal of cell biology. 1992; 119:749-761.
25. Derre I and Isberg RR. Legionella pneumophila Replication Vacuole Formation Involves Rapid Recruitment of Proteins of the Early Secretory System. Infect Immun. 2004; 72:3048-3053.
26. Kagan JC, Stein M-P, Pypaert M and Roy CR. Legionella Subvert the Functions of Rab1 and Sec22b to Create a Replicative Organelle. J Exp Med. 2004; 199:1201-1211.
27. Wu G, Yussman MG, Barrett TJ, Hahn HS, Osinska H, Hilliard GM, Wang X, Toyokawa T, Yatani A, Lynch RA, Robbins J and Dorn GW. Increased Myocardial Rab GTPase Expression: A Consequence and Cause of Cardiomyopathy. Circulation Research. 2001; 89:1130-1137.
28. Shimada K, Uzawa K, Kato M, Endo Y, Shiiba M, Bukawa H, Yokoe H, Seki N and Tanzawa H. Aberrant expression of RAB1A in human tongue cancer. Br J Cancer. 2005; 92:1915-1921.
29. Abraham RT. Making sense of amino acid sensing. Science. 2015; 347:128-129.
30. Sanchez-Gurmaches J and Guertin David A. mTORC1 gRABs the Golgi. Cancer Cell. 2014; 26:601-603.
31. Drenan RM, Liu X, Bertram PG and Zheng XFS. FKBP12-Rapamycin-associated Protein or Mammalian Target of Rapamycin (FRAP/mTOR) Localization in the Endoplasmic Reticulum and the Golgi Apparatus. J Biol Chem. 2004; 279:772-778.
32. Liu X and Zheng XFS. Endoplasmic Reticulum and Golgi Localization Sequences for Mammalian Target of Rapamycin. Mol Biol Cell. 2007; 18:1073-1082.
33. Kim E, Goraksha-Hicks P, Li L, Neufeld TP and Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008; 10:935-945.
34. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L and Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008; 320:1496-1501.
35. Tsang CK, Liu Y, Thomas J, Zhang Y and Zheng XFS. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun. 2014; 5.
36. Wu T-J, Wang X, Zhang Y, Meng L, Kerrigan John E, Burley Stephen K and Zheng XFS. Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase. Cell Reports. 2015; 11:446-459.