Different metabolic responses to PI3K inhibition in NSCLC cells harboring wild-type and G12C mutant KRAS

Oncotarget

Volumn 7, Issue 32, 2016, Pages 51462-51472

  Caiola, Elisa ^a   Brunelli, Laura ^a   Marabese, Mirko ^a   Broggini, Massimo ^a   Lupi, Monica ^a   Pastorelli, Roberta ^a  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

Author keywords

BEZ235; BKM120; KRAS; Metabolomics; NSCLC

Indexed keywords

AMMONIA; BUPARLISIB; CASPASE; CYTOSINE; DACTOLISIB; GLUTAMINE; GUANINE; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MUTANT PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B INHIBITOR; SERINE; CYSTEINE; GLYCINE; IMIDAZOLE DERIVATIVE; KRAS PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; PROTEIN P21; QUINOLINE DERIVATIVE;

AMMONIA FORMATION; ANTINEOPLASTIC ACTIVITY; ARTICLE; AUTOPHAGY; CELL CLONE; CELL GROWTH; CELLULAR DISTRIBUTION; ENZYME ACTIVATION; HUMAN; HUMAN CELL; NON SMALL CELL LUNG CANCER; PROTEIN METABOLISM; PROTEIN SYNTHESIS INHIBITION; SIGNAL TRANSDUCTION; WILD TYPE; AMINO ACID SUBSTITUTION; ANTAGONISTS AND INHIBITORS; CELL CULTURE; DRUG EFFECTS; GENETICS; LUNG TUMOR; METABOLISM; MISSENSE MUTATION; PATHOLOGY;

AMINO ACID SUBSTITUTION; CARCINOMA, NON-SMALL-CELL LUNG; CELLS, CULTURED; CYSTEINE; GLYCINE; HUMANS; IMIDAZOLES; LUNG NEOPLASMS; MUTATION, MISSENSE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS P21(RAS); QUINOLINES; SIGNAL TRANSDUCTION;

EID: 84982242171     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9849     Document Type: Article

References (40)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 277-300.
2. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small-cell lung cancer to smallcell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 2015; e165-72.
3. Piva S, Ganzinelli M, Garassino MC, Caiola E, Farina G, Broggini M, Marabese M. Across the universe of K-RAS mutations in non-small-cell-lung cancer. Curr Pharm Des. 2014; 3933-43.
4. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007; 295-308.
5. Garassino MC, Marabese M, Rusconi P, Rulli E, Martelli O, Farina G, Scanni A, Broggini M. Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer. Ann Oncol. 2011; 235-7.
6. Caiola E, Salles D, Frapolli R, Lupi M, Rotella G, Ronchi A, Garassino MC, Mattschas N, Colavecchio S, Broggini M, Wiesmuller L, Marabese M. Base excision repair-mediated resistance to cisplatin in KRAS(G12C) mutant NSCLC cells. Oncotarget. 2015; 30072-87. doi:10.18632/oncotarget.5019.
7. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the undruggable RAS: Mission possible? Nat Rev Drug Discov. 2014; 828-51.
8. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013; 548-51.
9. Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer. 2011; 761-74.
10. Castellano E, Downward J. RAS Interaction with PI3K: More Than Just Another Effector Pathway. Genes Cancer. 2011; 261-74. doi:10.1177/1947601911408079.
11. Castellano E, Sheridan C, Thin MZ, et al. Requirement for interaction of PI3-kinase p110alpha with RAS in lung tumor maintenance. Cancer Cell. 2013; 617-30.
12. Vanhaesebroeck B, Vogt PK, Rommel C. PI3K: from the bench to the clinic and back. Curr Top Microbiol Immunol. 2010; 1-19.
13. Davis WJ, Lehmann PZ, Li W. Nuclear PI3K signaling in cell growth and tumorigenesis. Front Cell Dev Biol. 2015; 24.
14. Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep. 2015; 841-51.
15. Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015; 36-54.
16. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005; 988-1004.
17. Caino MC, Ghosh JC, Chae YC, et al. PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion. Proc Natl Acad Sci U S A. 2015; 8638-43.
18. Ghosh JC, Siegelin MD, Vaira V, et al. Adaptive mitochondrial reprogramming and resistance to PI3K therapy. J Natl Cancer Inst. 2015;
19. Serizawa M, Kusuhara M, Zangiacomi V, Urakami K, Watanabe M, Takahashi T, Yamaguchi K, Yamamoto N, Koh Y. Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells. Anticancer Res. 2014; 2779-87.
20. Sun Y, Daemen A, Hatzivassiliou G, Arnott D, Wilson C, Zhuang G, Gao M, Liu P, Boudreau A, Johnson L, Settleman J. Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells. Cancer Metab. 2014; 20.
21. Howell JJ, Manning BD. mTOR couples cellular nutrient sensing to organismal metabolic homeostasis. Trends Endocrinol Metab. 2011; 94-102.
22. Dibble CC, Cantley LC. Regulation of mTORC1 by PI3K signaling. Trends Cell Biol. 2015; 545-55.
23. Brunelli L, Caiola E, Marabese M, Broggini M, Pastorelli R. Capturing the metabolomic diversity of KRAS mutants in non-small-cell lung cancer cells. Oncotarget. 2014; 4722-31. doi:10.18632/oncotarget.1958.
24. Xu CX, Zhao L, Yue P, Fang G, Tao H, Owonikoko TK, Ramalingam SS, Khuri FR, Sun SY. Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells by blockage of autophagy. Cancer Biol Ther. 2011; 549-55.
25. Qu Y, Wu X, Yin Y, Yang Y, Ma D, Li H. Antitumor activity of selective MEK1/2 inhibitor AZD6244 in combination with PI3K/mTOR inhibitor BEZ235 in gefitinib-resistant NSCLC xenograft models. J Exp Clin Cancer Res. 2014; 52.
26. Zito CR, Jilaveanu LB, Anagnostou V, Rimm D, Bepler G, Maira SM, Hackl W, Camp R, Kluger HM, Chao HH. Multi-level targeting of the phosphatidylinositol-3-kinase pathway in non-small cell lung cancer cells. PLoS One. 2012; e31331.
27. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A. 2008; 18782-7.
28. Eng CH, Abraham RT. Glutaminolysis yields a metabolic by-product that stimulates autophagy. Autophagy. 2010; 968-70.
29. Polletta L, Vernucci E, Carnevale I, et al. SIRT5 regulation of ammonia-induced autophagy and mitophagy. Autophagy. 2015; 253-70.
30. Marabese M, Rulli E, Bettini A, Garassino MC, Longo F, Moscetti L, Pavese I, Lauricella C, Broggini M, Farina G. KRAS mutational status impact progression-free survival of patients treated with platinum-based chemotherapy in NSCLC. Molecular Cancer Therapeutics. 2011; B77.
31. Costa C, Ebi H, Martini M, et al. Measurement of PIP3 levels reveals an unexpected role for p110beta in early adaptive responses to p110alpha-specific inhibitors in luminal breast cancer. Cancer Cell. 2015; 97-108.
32. Juric D, Castel P, Griffith M, et al. Convergent loss of PTEN leads to clinical resistance to a PI(3) Kalpha inhibitor. Nature. 2015; 240-4.
33. Locasale JW. Metabolic rewiring drives resistance to targeted cancer therapy. Mol Syst Biol. 2012; 597.
34. Meng M, Chen S, Lao T, Liang D, Sang N. Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells. Cell Cycle. 2010; 3921-32.
35. Kalhan SC, Hanson RW. Resurgence of serine: an often neglected but indispensable amino Acid. J Biol Chem. 2012; 19786-91.
36. Gravel SP, Hulea L, Toban N, Birman E, Blouin MJ, Zakikhani M, Zhao Y, Topisirovic I, St-Pierre J, Pollak M. Serine deprivation enhances antineoplastic activity of biguanides. Cancer Res. 2014; 7521-33.
37. Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013; 542-6.
38. Amelio I, Cutruzzola F, Antonov A, Agostini M, Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci. 2014; 191-8.
39. Altman BJ, Rathmell JC. Metabolic stress in autophagy and cell death pathways. Cold Spring Harb Perspect Biol. 2012; a008763.
40. Marabese M, Marchini S, Sabatino MA, Polato F, Vikhanskaya F, Marrazzo E, Riccardi E, Scanziani E, Broggini M. Effects of inducible overexpression of DNp73alpha on cancer cell growth and response to treatment in vitro and in vivo. Cell Death Differ. 2005; 805-14.