mTORC1 upregulation via ERK-dependent gene expression change confers intrinsic resistance to MEK inhibitors in oncogenic KRas-mutant cancer cells

Oncogene

Volumn 34, Issue 45, 2015, Pages 5607-5616

  Komatsu, N ^a   Fujita, Y ^a   Matsuda, M ^a   Aoki, K ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; 2 [4 (2 DIMETHYLAMINOETHOXY)PHENYL] 4 (1 HYDROXYIMINO 5 INDANYL) 5 (4 PYRIDINYL) 1H IMIDAZOLE; B RAF KINASE; BI D 1870; DEPTOR PROTEIN; GEFITINIB; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE INHIBITOR; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN; RAPAMYCIN; S6 KINASE; SELUMETINIB; TORIN1; TSC1 PROTEIN; TUBERIN; UNCLASSIFIED DRUG; BRAF PROTEIN, HUMAN; DEPTOR PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE INHIBITOR; RAS PROTEIN; SIGNAL PEPTIDE; TARGET OF RAPAMYCIN KINASE; TELOMERASE; TERT PROTEIN, HUMAN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; CANCER CELL LINE; CANCER RESISTANCE; CELL GROWTH; CELL MUTANT; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME INHIBITION; ENZYME KINETICS; ENZYME PHOSPHORYLATION; ENZYME REPRESSION; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE CONTROL; GENE EXPRESSION; HUMAN; HUMAN CELL; IC50; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROCESSING; RECEPTOR DOWN REGULATION; RECEPTOR UPREGULATION; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MUTATION; NEOPLASMS; TUMOR CELL LINE; UPREGULATION;

CELL LINE, TUMOR; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MAP KINASE SIGNALING SYSTEM; MULTIPROTEIN COMPLEXES; MUTATION; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS B-RAF; RAS PROTEINS; TELOMERASE; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS; UP-REGULATION;

EID: 84947031736     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2015.16     Document Type: Article

References (40)

1. Nishida E, Gotoh Y. The MAP kinase cascade is essential for diverse signal transduction pathways. Trends Biochem Sci 1993; 18: 128-131
2. Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 2011; 11: 761-774
3. Weinstein IB. Cancer. Addiction to oncogenes-The Achilles heal of cancer. Science 2002; 297: 63-64
4. Sharma SV, Settleman J. Oncogene addiction: setting the stage for molecularly targeted cancer therapy. Genes Dev 2007; 21: 3214-3231
5. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7: 169-181
6. Neuzillet C, Tijeras-Raballand A, de Mestier L, Cros J, Faivre S, Raymond E. MEK in cancer and cancer therapy. Pharmacol Ther 2014; 141: 160-171
7. Solit DB, Garraway LA, Pratilas CA, Sawai A, Getz G, Basso A, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006; 439: 358-362
8. Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, et al. A gene expression signature associated with ?K-Ras addiction? reveals regulators of EMT and tumor cell survival. Cancer Cell 2009; 15: 489-500
9. Rebucci M, Michiels C. Molecular aspects of cancer cell resistance to chemotherapy. Biochem Pharmacol 2013; 85: 1219-1226
10. Sos ML, Fischer S, Ullrich R, Peifer M, Heuckmann JM, Koker M, et al. Identifying genotype-dependent efficacy of single and combined PI3K-And MAPK-pathway inhibition in cancer. Proc Natl Acad Sci USA 2009; 106: 18351-18356
11. Klinger B, Sieber A, Fritsche-Guenther R, Witzel F, Berry L, Schumacher D, et al. Network quantification of EGFR signaling unveils potential for targeted combination therapy. Mol Syst Biol 2013; 9: 673
12. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 2012; 483: 100-103
13. Hatzivassiliou G, Haling JR, Chen H, Song K, Price S, Heald R, et al. Mechanism of MEK inhibition determines efficacy in mutant KRAS-versus BRAF-driven cancers. Nature 2013; 501: 232-236
14. Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA 2009; 106: 4519-4524
15. Mirzoeva OK, Das D, Heiser LM, Bhattacharya S, Siwak D, Gendelman R, et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res 2009; 69: 565-572
16. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008; 14: 1351-1356
17. Bean GR, Ganesan YT, Dong Y, Takeda S, Liu H, Chan PM, et al. PUMA and BIM are required for oncogene inactivation-induced apoptosis. Sci Signal 2013. 6-ra20
18. LoRusso P, Shapiro G, Pandya SS, Kwak EL, Jones C, Belvin M, et al. A first-in-human phase Ib study to evaluate the MEK inhibitor GDC-0973, combined with the pan-PI3K inhibitor GDC-0941, in patients with advanced solid tumors. J Clin Oncol 2012. 30
19. Speranza G, Kinders RJ, Khin S, MK Weil, Do KT, Horneffer Y, et al. Pharmacodynamic biomarker-driven trial of MK-2206, an AKT inhibitor, with AZD6244 (selumetinib), a MEK inhibitor, in patients with advanced colorectal carcinoma (CRC). J Clin Oncol 2012. 30
20. Komatsu N, Aoki K, Yamada M, Yukinaga H, Fujita Y, Kamioka Y, et al. Development of an optimized backbone of FRET biosensors for kinases and GTPases. Mol Biol Cell 2011; 22: 4647-4656
21. Friday BB, Yu C, Dy GK, Smith PD, Wang L, Thibodeau SN, et al. BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. Cancer Res 2008; 68: 6145-6153
22. LoRusso PM, Krishnamurthi SS, Rinehart JJ, Nabell LM, Malburg L, Chapman PB, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin Cancer Res 2010; 16: 1924-1937
23. Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009; 284: 8023-8032
24. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, et al. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 2010; 18: 39-51
25. Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, Waterfield MD, Downward J. Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation. EMBO J 1996; 15: 2442-2451
26. Mendoza MC, Er EE, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-Talk and compensation. Trends Biochem Sci 2011; 36: 320-328
27. Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci USA 2004; 101: 13489-13494
28. Carriere A, Romeo Y, Acosta-Jaquez HA, Moreau J, Bonneil E, Thibault P, et al. ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem 2011; 286: 567-577
29. Corcoran RB, Rothenberg SM, Hata AN, Faber AC, Piris A, Nazarian RM, et al. TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma. Sci Transl Med 2013; 5196ra198
30. Yusa K, Rad R, Takeda J, Bradley A. Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat Methods 2009; 6: 363-369
31. Kawakami K, Noda T. Transposition of the Tol2 element, an Ac-like element from the Japanese medaka fish Oryzias latipes, in mouse embryonic stem cells. Genetics 2004; 166: 895-899
32. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM. Development of a self-inactivating lentivirus vector. J Virol 1998; 72: 8150-8157
33. Akagi T, Sasai K, Hanafusa H. Refractory nature of normal human diploid fibroblasts with respect to oncogene-mediated transformation. Proc Natl Acad Sci USA 2003; 100: 13567-13572
34. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002; 110: 163-175
35. Aoki K, Matsuda M. Visualization of small GTPase activity with fluorescence resonance energy transfer-based biosensors. Nat Protoc 2009; 4: 1623-1631
36. Otsu N. A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern 1979; 9: 62-66
37. Fujita Y, Komatsu N, Matsuda M, Aoki K. Fluorescence resonance energy transfer based quantitative analysis of feedforward and feedback loops in epidermal growth factor receptor signaling and the sensitivity to molecular targeting drugs. FEBS J 2014; 281: 3177-3192
38. Corcoran RB, Dias-Santagata D, Bergethon K, Iafrate AJ, Settleman J, Engelman JA. BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci Signal 2010. 3-ra84
39. Aoki K, Kumagai Y, Sakurai A, Komatsu N, Fujita Y, Shionyu C, et al. Stochastic ERK activation induced by noise and cell-To-cell propagation regulates cell density-dependent proliferation. Mol Cell 2013; 52: 529-540
40. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 2008; 5: 621-628