Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer

Nature Communications

Volumn 7, Issue , 2016, Pages

  Hao, Yujun ^a,b   Samuels, Yardena ^c,d   Li, Qingling ^b   Krokowski, Dawid ^a   Guan, Bo Jhih ^a   Wang, Chao ^a,b,k   Jin, Zhicheng ^b   Dong, Bohan ^a,e   Cao, Bo ^a,f   Feng, Xiujing ^a,b   Xiang, Min ^a,g   Xu, Claire ^h   Fink, Stephen ^a,b   Meropol, Neal J ⁱ   Xu, Yan ^a,b   Conlon, Ronald A ^a,b   Markowitz, Sanford ^a,b   Kinzler, Kenneth W ^c   Velculescu, Victor E ^c   Brunengraber, Henri ^b   Willis, Joseph E ^j   Laframboise, Thomas ^a,b   Hatzoglou, Maria ^a   Zhang, Guo Fang ^b   Vogelstein, Bert ^c   Wang, Zhenghe ^a,b   more..

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

^c JOHNS HOPKINS UNIVERSITY   (United States)

^d WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^e WANNAN MEDICAL COLLEGE   (China)

^f THIRD MILITARY MEDICAL UNIVERSITY   (China)

^g Suzhou Health College   (China)

^h Hathaway Brown School   (United States)

ⁱ CLEVELAND STATE UNIVERSITY   (United States)

^j UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^k DIVISION OF MEDICAL ONCOLOGY   (Singapore)

more..

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOGLUTARIC ACID; ACTIVATING TRANSCRIPTION FACTOR 4; ALANINE AMINOTRANSFERASE; AMINOOXYACETIC ACID; DEUBIQUITINASE; GENOMIC DNA; GLUCOSE; GLUTAMINE; K RAS PROTEIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PHOSPHOINOSITIDE DEPENDENT PROTEIN KINASE 1; PIK3CA PROTEIN; PROTEIN; PROTEIN NOXA; PROTEIN P110; PROTEIN P110ALPHA; PUMA PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE; RSK2 PROTEIN; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR FKHR; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; ADENOSINE TRIPHOSPHATE; ALPHA-KETOGLUTARIC ACID; AMINOTRANSFERASE; ANTINEOPLASTIC AGENT; ATF4 PROTEIN, HUMAN; ENZYME INHIBITOR; GPT2 PROTEIN, HUMAN; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PIK3CA PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; PYRUVATE DEHYDROGENASE (ACETYL-TRANSFERRING) KINASE;

AMINO ACID; BIOCHEMISTRY; BIOLOGICAL ANALYSIS; CANCER; CRASSULACEAN ACID METABOLISM; ENZYME ACTIVITY; GENE EXPRESSION; METABOLISM; MUTATION;

ALLELE; AMINO ACID METABOLISM; APOPTOSIS; ARTICLE; BINDING AFFINITY; CANCER INHIBITION; CELL METABOLISM; CELL PROLIFERATION; CELL SURVIVAL; CITRIC ACID CYCLE; CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEAT; COLORECTAL CANCER; CONTROLLED STUDY; ENZYME ACTIVITY; GENE INACTIVATION; GENE MUTATION; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; HUMAN TISSUE; MYRISTYLATION; OPEN READING FRAME; PROTEIN PHOSPHORYLATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION SITE; TRANSLATION INITIATION; UBIQUITINATION; UPREGULATION; WESTERN BLOTTING; WILD TYPE; ADENOCARCINOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; COLORECTAL TUMOR; DRUG EFFECT; DRUG SCREENING; ENZYMOLOGY; FEMALE; GENE EXPRESSION REGULATION; GENETICS; HCT 116 CELL LINE; HT-29 CELL LINE; METABOLISM; MOUSE; MUTATION; NUDE MOUSE; PATHOLOGY; TUMOR CELL LINE; TUMOR VOLUME;

ACTIVATING TRANSCRIPTION FACTOR 4; ADENOCARCINOMA; ADENOSINE TRIPHOSPHATE; AMINOOXYACETIC ACID; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CITRIC ACID CYCLE; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; COLORECTAL NEOPLASMS; ENZYME INHIBITORS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUTAMINE; HCT116 CELLS; HT29 CELLS; HUMANS; KETOGLUTARIC ACIDS; MICE; MICE, NUDE; MUTATION; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; TRANSAMINASES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84975460924     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms11971     Document Type: Article

References (44)

1. Dang, C. V. Links between metabolism and cancer. Genes Dev. 26, 877-890 (2012).
2. Vander Heiden, M. G., Cantley, L. C., Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033 (2009).
3. Abraham, R. T., Eng, C. H. A metabolic (re-)balancing act. Mol. Cell 38, 481-482 (2010).
4. Hensley, C. T., Wasti, A. T., DeBerardinis, R. J. Glutamine and cancer: cell biology, physiology, and clinical opportunities. J. Clin. Invest. 123, 3678-3684 (2013).
5. Gao, P. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458, 762-765 (2009).
6. Qing, G. et al. ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22, 631-644 (2012).
7. Reynolds, M. R. et al. Control of glutamine metabolism by the tumor suppressor Rb. Oncogene 33, 556-566 (2014).
8. Suzuki, S. et al. Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc. Natl. Acad. Sci. USA 107, 7461-7466 (2010).
9. Jiang, P., Du, W., Mancuso, A., Wellen, K. E., Yang, X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493, 689-693 (2013).
10. Gameiro, P. A. et al. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 17, 372-385 (2013).
11. Son, J. et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496, 101-105 (2013).
12. Cantley, L. C. The phosphoinositide 3-kinase pathway. Science 296, 1655-1657 (2002).
13. Hao, Y., Zhao, S., Wang, Z. Targeting the protein-protein interaction between IRS1 and mutant p110alpha for cancer therapy. Toxicol. Pathol. 42, 140-147 (2014).
14. Samuels, Y. et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554 (2004).
15. Lawrence, M. S. et al. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505, 495-501 (2014).
16. Zhao, L., Vogt, P. K. Class I PI3K in oncogenic cellular transformation. Oncogene 27, 5486-5496 (2008).
17. Samuels, Y. et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-573 (2005).
18. Leithner, K. et al. PCK2 activation mediates an adaptive response to glucose depletion in lung cancer. Oncogene 34, 1044-1050 (2015).
19. Vincent, E. E. et al. Mitochondrial phosphoenolpyruvate carboxykinase regulates metabolic adaptation and enables glucose-independent tumor growth. Mol. Cell 60, 195-207 (2015).
20. Yun, J. et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325, 1555-1559 (2009).
21. Velculescu, V. E., Zhang, L., Vogelstein, B., Kinzler, K. W. Serial analysis of gene expression. Science 270, 484-487 (1995).
22. Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318, 1108-1113 (2007).
23. Thornburg, J. M. et al. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res. 10, R84 (2008).
24. Csibi, A. et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153, 840-854 (2013).
25. Guan, B. J. et al. Translational control during endoplasmic reticulum stress beyond phosphorylation of the translation initiation factor eIF2alpha. J. Biol. Chem. 289, 12593-12611 (2014).
26. Yang, X. et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 117, 387-398 (2004).
27. Frodin, M. et al. A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation. The EMBO J. 21, 5396-5407 (2002).
28. Weinberg, F. et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl Acad. Sci. USA 107, 8788-8793 (2010).
29. Tuveson, D. A. et al. Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 5, 375-387 (2004).
30. Arena, S. et al. Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers. Cancer Res. 67, 8468-8476 (2007).
31. Castellano, E., Downward, J. RAS Interaction with PI3K: more than just another effector pathway. Genes Cancer 2, 261-274 (2011).
32. Taniguchi, C. M. et al. Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta. Cell Metab. 3, 343-353 (2006).
33. Hu, H. et al. Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton. Cell 164, 433-446 (2016).
34. Engelman, J. A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550-562 (2009).
35. Vadas, O., Burke, J. E., Zhang, X., Berndt, A., Williams, R. L. Structural basis for activation and inhibition of class I phosphoinositide 3-kinases. Sci. Signal. 4: re2 (2011).
36. Costa, C. et al. Measurement of PIP Levels reveals an unexpected role for p110bemta in early adaptive responses to p110alpha-specific inhibitors in luminal breast cancer. Cancer Cell 27, 97-108 (2014).
37. Lindblom, P. et al. Isoforms of alanine aminotransferases in human tissues and serum-differential tissue expression using novel antibodies. Arch. Biochem. Biophys. 466, 66-77 (2007).
38. Klempner, S. J., Myers, A. P., Cantley, L. C. What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway. Cancer Discov. 3, 1345-1354 (2013).
39. Ericson, K. et al. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. Proc. Natl. Acad. Sci. USA 107, 2598-2603 (2010).
40. Li, B., Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011).
41. Zhang, X. et al. Epitope tagging of endogenous proteins for genome-wide ChIP-chip studies. Nat. Methods 5, 163-165 (2008).
42. Hao, Y. et al. Gain of interaction with IRS1 by p110alpha-helical domain mutants is crucial for their oncogenic functions. Cancer Cell 23, 583-593 (2013).
43. Du, Z. et al. DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. Sci. Signal. 3, ra80 (2010).
44. Zhao, Y. et al. Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T. Proc. Natl. Acad. Sci. USA 107, 2592-2597 (2010).