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Erschienen in: International Journal of Clinical Oncology 4/2017

24.06.2017 | Review Article

Targeting metabolic reprogramming in KRAS-driven cancers

verfasst von: Kenji Kawada, Kosuke Toda, Yoshiharu Sakai

Erschienen in: International Journal of Clinical Oncology | Ausgabe 4/2017

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Abstract

Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect. The role of KRAS signaling in the regulation of aerobic glycolysis has been reported in several types of cancer. KRAS-driven cancers are characterized by altered metabolic pathways involving enhanced nutrients uptake, enhanced glycolysis, enhanced glutaminolysis, and elevated synthesis of fatty acids and nucleotides. However, Just how mutated KRAS can coordinate the metabolic shift to promote tumor growth and whether specific metabolic pathways are essential for the tumorigenesis of KRAS-driven cancers are questions which remain to be answered. In this context, the aim of this review is to summarize current data on KRAS-related metabolic alterations in cancer cells. Given that cancer cells rely on changes in metabolism to support their growth and survival, the targeting of metabolic processes may be a potential strategy for treating KRAS-driven cancers.
Literatur
1.
Zurück zum Zitat Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033CrossRefPubMedPubMedCentral Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029–1033CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11:325–337CrossRefPubMed Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer 11:325–337CrossRefPubMed
3.
Zurück zum Zitat Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95CrossRefPubMed Cairns RA, Harris IS, Mak TW (2011) Regulation of cancer cell metabolism. Nat Rev Cancer 11:85–95CrossRefPubMed
4.
Zurück zum Zitat Galluzzi L, Kepp O, Vander Heiden MG et al (2013) Metabolic targets for cancer therapy. Nat Rev Drug Discov 12:829–846CrossRefPubMed Galluzzi L, Kepp O, Vander Heiden MG et al (2013) Metabolic targets for cancer therapy. Nat Rev Drug Discov 12:829–846CrossRefPubMed
5.
8.
9.
Zurück zum Zitat Kovacević Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32:326–333PubMed Kovacević Z, Morris HP (1972) The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 32:326–333PubMed
12.
16.
Zurück zum Zitat Commisso C, Davidson SM, Soydaner-Azeloglu RG et al (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633–637CrossRefPubMedPubMedCentral Commisso C, Davidson SM, Soydaner-Azeloglu RG et al (2013) Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497:633–637CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Ying H, Kimmelman AC, Lyssiotis CA et al (2012) Oncogenic KRAS maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149:656–670CrossRefPubMedPubMedCentral Ying H, Kimmelman AC, Lyssiotis CA et al (2012) Oncogenic KRAS maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149:656–670CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Csibi A, Lee G, Yoon SO et al (2014) The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol 24:2274–2280CrossRefPubMedPubMedCentral Csibi A, Lee G, Yoon SO et al (2014) The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol 24:2274–2280CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat DeBerardinis RJ, Cheng T (2010) Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29:313–324CrossRefPubMed DeBerardinis RJ, Cheng T (2010) Q’s next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 29:313–324CrossRefPubMed
21.
Zurück zum Zitat Bhutia YD, Babu E, Ramachandran S et al (2015) Amino acid transporters in cancer and their relevance to “glutamine addiction”: novel targets for the design of a new class of anticancer drugs. Cancer Res 75:1782–1788CrossRefPubMed Bhutia YD, Babu E, Ramachandran S et al (2015) Amino acid transporters in cancer and their relevance to “glutamine addiction”: novel targets for the design of a new class of anticancer drugs. Cancer Res 75:1782–1788CrossRefPubMed
22.
Zurück zum Zitat Son J, Lyssiotis CA, Ying H et al (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496:101–105CrossRefPubMedPubMedCentral Son J, Lyssiotis CA, Ying H et al (2013) Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature 496:101–105CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Wang YP, Zhou W, Wang J et al (2016) Arginine methylation of MDH1 by CARM1 inhibits glutamine metabolism and suppresses pancreatic cancer. Mol Cell 64:673–687CrossRefPubMed Wang YP, Zhou W, Wang J et al (2016) Arginine methylation of MDH1 by CARM1 inhibits glutamine metabolism and suppresses pancreatic cancer. Mol Cell 64:673–687CrossRefPubMed
24.
Zurück zum Zitat Mayers JR, Wu C, Clish CB et al (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193–1198CrossRefPubMedPubMedCentral Mayers JR, Wu C, Clish CB et al (2014) Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med 20:1193–1198CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Mayers JR, Torrence ME, Danai LV et al (2016) Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science 353:1161–1165CrossRefPubMedPubMedCentral Mayers JR, Torrence ME, Danai LV et al (2016) Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science 353:1161–1165CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Guo JY, Chen HY, Mathew R et al (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:460–470CrossRefPubMedPubMedCentral Guo JY, Chen HY, Mathew R et al (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev 25:460–470CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Eng CH, Wang Z, Tkach D et al (2016) Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc Natl Acad Sci USA 113:182–187CrossRefPubMed Eng CH, Wang Z, Tkach D et al (2016) Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc Natl Acad Sci USA 113:182–187CrossRefPubMed
30.
Zurück zum Zitat Rosenfeld MR, Ye X, Supko JG et al (2014) A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 10:1359–1368CrossRefPubMedPubMedCentral Rosenfeld MR, Ye X, Supko JG et al (2014) A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 10:1359–1368CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Mahalingam D, Mita M, Sarantopoulos J et al (2014) Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy 10:1403–1414CrossRefPubMedPubMedCentral Mahalingam D, Mita M, Sarantopoulos J et al (2014) Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors. Autophagy 10:1403–1414CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Wolpin BM, Rubinson DA, Wang X et al (2014) Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist 19:637–638CrossRefPubMedPubMedCentral Wolpin BM, Rubinson DA, Wang X et al (2014) Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist 19:637–638CrossRefPubMedPubMedCentral
33.
34.
Zurück zum Zitat Kamphorst JJ, Cross JR, Fan J et al (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci USA 110:8882–8887CrossRefPubMedPubMedCentral Kamphorst JJ, Cross JR, Fan J et al (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc Natl Acad Sci USA 110:8882–8887CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799CrossRefPubMed Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789–799CrossRefPubMed
36.
Zurück zum Zitat Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancers. N Engl J Med 359:1757–1765CrossRefPubMed Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancers. N Engl J Med 359:1757–1765CrossRefPubMed
37.
Zurück zum Zitat Lievre A, Bachet JB, Boige V et al (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26:374–379CrossRefPubMed Lievre A, Bachet JB, Boige V et al (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26:374–379CrossRefPubMed
39.
Zurück zum Zitat Yun J, Rago C, Cheong I et al (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325:1555–1559CrossRefPubMedPubMedCentral Yun J, Rago C, Cheong I et al (2009) Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 325:1555–1559CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Jadvar H, Alavi A, Gambhir SS (2009) 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med 50:1820–1827CrossRefPubMedPubMedCentral Jadvar H, Alavi A, Gambhir SS (2009) 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization. J Nucl Med 50:1820–1827CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Kawada K, Nakamoto Y, Kawada M et al (2012) Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res 18:1696–1703CrossRefPubMed Kawada K, Nakamoto Y, Kawada M et al (2012) Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res 18:1696–1703CrossRefPubMed
42.
Zurück zum Zitat Kawada K, Toda K, Nakamoto Y et al (2015) Relationship between 18F-FDG PET/CT scans and KRAS mutations in metastatic colorectal cancer. J Nucl Med 56:1322–1327CrossRefPubMed Kawada K, Toda K, Nakamoto Y et al (2015) Relationship between 18F-FDG PET/CT scans and KRAS mutations in metastatic colorectal cancer. J Nucl Med 56:1322–1327CrossRefPubMed
43.
44.
Zurück zum Zitat Chen SW, Chiang HC, Chen WT et al (2014) Correlation between PET/CT parameters and KRAS expression in colorectal cancer. Clin Nucl Med 39:685–689CrossRefPubMed Chen SW, Chiang HC, Chen WT et al (2014) Correlation between PET/CT parameters and KRAS expression in colorectal cancer. Clin Nucl Med 39:685–689CrossRefPubMed
45.
Zurück zum Zitat Miles KA, Ganeshan B, Rodriguez-Justo M et al (2014) Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer. J Nucl Med 55:386–391CrossRefPubMed Miles KA, Ganeshan B, Rodriguez-Justo M et al (2014) Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer. J Nucl Med 55:386–391CrossRefPubMed
46.
Zurück zum Zitat Lee JH, Kang J, Baik SH et al (2016) Relationship between 18F-Fluorodeoxyglucose uptake and V-Ki-Ras2 kirsten rat sarcoma viral oncogene homolog mutation in colorectal cancer patients: variability depending on c-reactive protein level. Medicine 95:e2236CrossRefPubMedPubMedCentral Lee JH, Kang J, Baik SH et al (2016) Relationship between 18F-Fluorodeoxyglucose uptake and V-Ki-Ras2 kirsten rat sarcoma viral oncogene homolog mutation in colorectal cancer patients: variability depending on c-reactive protein level. Medicine 95:e2236CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Caicedo C, Garcia-Velloso MJ, Lozano MD et al (2014) Role of [1∙F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer. Eur J Nucl Med Mol Imaging 41:2058–2065CrossRefPubMed Caicedo C, Garcia-Velloso MJ, Lozano MD et al (2014) Role of [1∙F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer. Eur J Nucl Med Mol Imaging 41:2058–2065CrossRefPubMed
48.
Zurück zum Zitat Iwamoto M, Kawada K, Nakamoto Y et al (2014) Regulation of 18F-FDG accumulation in colorectal cancer cells with mutated KRAS. J Nucl Med 55:2038–2044CrossRefPubMed Iwamoto M, Kawada K, Nakamoto Y et al (2014) Regulation of 18F-FDG accumulation in colorectal cancer cells with mutated KRAS. J Nucl Med 55:2038–2044CrossRefPubMed
49.
Zurück zum Zitat Yun J, Mullarky E, Lu C et al (2015) Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350:1391–1396CrossRefPubMedPubMedCentral Yun J, Mullarky E, Lu C et al (2015) Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350:1391–1396CrossRefPubMedPubMedCentral
50.
Zurück zum Zitat Aguilera O, Muñoz-Sagastibelza M, Torrejón B et al (2016) Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget 7:47954–47965CrossRefPubMedPubMedCentral Aguilera O, Muñoz-Sagastibelza M, Torrejón B et al (2016) Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer. Oncotarget 7:47954–47965CrossRefPubMedPubMedCentral
51.
Zurück zum Zitat Toda K, Kawada K, Iwamoto M et al (2016) Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia 18:654–665CrossRefPubMedPubMedCentral Toda K, Kawada K, Iwamoto M et al (2016) Metabolic alterations caused by KRAS mutations in colorectal cancer contribute to cell adaptation to glutamine depletion by upregulation of asparagine synthetase. Neoplasia 18:654–665CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Zhang J, Fan J, Venneti S et al (2014) Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell 56:205–218CrossRefPubMedPubMedCentral Zhang J, Fan J, Venneti S et al (2014) Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell 56:205–218CrossRefPubMedPubMedCentral
54.
Zurück zum Zitat Ye J, Kumanova M, Hart LS et al (2010) The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J 29:2082–2096CrossRefPubMedPubMedCentral Ye J, Kumanova M, Hart LS et al (2010) The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation. EMBO J 29:2082–2096CrossRefPubMedPubMedCentral
55.
Zurück zum Zitat Balasubramanian MN, Butterworth EA, Kilberg MS (2013) Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab 304:789–799CrossRef Balasubramanian MN, Butterworth EA, Kilberg MS (2013) Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab 304:789–799CrossRef
56.
Zurück zum Zitat Dufour E, Gay F, Aguera K et al (2012) Pancreatic tumor sensitivity to plasma l-asparagine starvation. Pancreas 41:940–948CrossRefPubMed Dufour E, Gay F, Aguera K et al (2012) Pancreatic tumor sensitivity to plasma l-asparagine starvation. Pancreas 41:940–948CrossRefPubMed
58.
Zurück zum Zitat Ikeuchi H, Ahn YM, Otokawa T et al (2012) A sulfoximine-based inhibitor of human asparagine synthetase kills l-asparaginase-resistant leukemia cells. Bioorg Med Chem 20:5915–5927CrossRefPubMed Ikeuchi H, Ahn YM, Otokawa T et al (2012) A sulfoximine-based inhibitor of human asparagine synthetase kills l-asparaginase-resistant leukemia cells. Bioorg Med Chem 20:5915–5927CrossRefPubMed
59.
Zurück zum Zitat Kral AS, Xu S, Graeber TG et al (2016) Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun 7:11457CrossRef Kral AS, Xu S, Graeber TG et al (2016) Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun 7:11457CrossRef
60.
Zurück zum Zitat Weinberg F, Hamanaka R, Wheaton WW et al (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107:8788–8793CrossRefPubMedPubMedCentral Weinberg F, Hamanaka R, Wheaton WW et al (2010) Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 107:8788–8793CrossRefPubMedPubMedCentral
61.
Zurück zum Zitat Wong CC, Qian Y, Li X et al (2016) SLC25A22 promotes proliferation and survival of colorectal cancer cells with KRAS mutations and xenograft tumor progression in mice via intracellular synthesis of aspartate. Gastroenterology 151(945–960):e6 Wong CC, Qian Y, Li X et al (2016) SLC25A22 promotes proliferation and survival of colorectal cancer cells with KRAS mutations and xenograft tumor progression in mice via intracellular synthesis of aspartate. Gastroenterology 151(945–960):e6
63.
Zurück zum Zitat Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol 15:254–266CrossRefPubMed Fuchs BC, Bode BP (2005) Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Semin Cancer Biol 15:254–266CrossRefPubMed
64.
Zurück zum Zitat Bhutia YD, Ganapathy V (2016) Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta 1863:2531–2539CrossRefPubMed Bhutia YD, Ganapathy V (2016) Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta 1863:2531–2539CrossRefPubMed
65.
67.
Zurück zum Zitat Patra KC, Wang Q, Bhaskar PT et al (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24:213–228CrossRefPubMedPubMedCentral Patra KC, Wang Q, Bhaskar PT et al (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell 24:213–228CrossRefPubMedPubMedCentral
68.
Zurück zum Zitat Jain M, Nilsson R, Sharma S et al (2012) Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336:1040–1044CrossRefPubMedPubMedCentral Jain M, Nilsson R, Sharma S et al (2012) Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 336:1040–1044CrossRefPubMedPubMedCentral
69.
Zurück zum Zitat Kim D, Fiske BP, Birsoy K et al (2015) SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature 520:363–367CrossRefPubMedPubMedCentral Kim D, Fiske BP, Birsoy K et al (2015) SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature 520:363–367CrossRefPubMedPubMedCentral
70.
Zurück zum Zitat Guo JY, Karsli-Uzunbas G, Mathew R et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461CrossRefPubMedPubMedCentral Guo JY, Karsli-Uzunbas G, Mathew R et al (2013) Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis. Genes Dev 27:1447–1461CrossRefPubMedPubMedCentral
71.
Zurück zum Zitat Padanad MS, Konstantinidou G, Venkateswaran N (2016) Fatty acid oxidation mediated by Acyl-CoA synthetase long chain 3 is required for mutant KRAS lung tumorigenesis. Cell Rep 16:1614–1628CrossRefPubMedPubMedCentral Padanad MS, Konstantinidou G, Venkateswaran N (2016) Fatty acid oxidation mediated by Acyl-CoA synthetase long chain 3 is required for mutant KRAS lung tumorigenesis. Cell Rep 16:1614–1628CrossRefPubMedPubMedCentral
72.
Zurück zum Zitat Gouw AM, Eberlin LS, Margulis K (2017) Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc Natl Acad Sci USA 114:4300–4305CrossRefPubMed Gouw AM, Eberlin LS, Margulis K (2017) Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc Natl Acad Sci USA 114:4300–4305CrossRefPubMed
73.
Zurück zum Zitat Davidson SM, Papagiannakopoulos T, Olenchzock BA et al (2016) Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer. Cell Metab 23:517–528CrossRefPubMedPubMedCentral Davidson SM, Papagiannakopoulos T, Olenchzock BA et al (2016) Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer. Cell Metab 23:517–528CrossRefPubMedPubMedCentral
74.
Zurück zum Zitat Zhou B, Der CJ, Cox AD (2016) The role of wild type RAS isoforms in cancer. Semin Cell Dev Biol 58:60–69CrossRefPubMed Zhou B, Der CJ, Cox AD (2016) The role of wild type RAS isoforms in cancer. Semin Cell Dev Biol 58:60–69CrossRefPubMed
75.
Zurück zum Zitat Ratnikov BI, Scott DA, Osterman AL (2017) Metabolic rewiring in melanoma. Oncogene 36:147–157CrossRefPubMed Ratnikov BI, Scott DA, Osterman AL (2017) Metabolic rewiring in melanoma. Oncogene 36:147–157CrossRefPubMed
Metadaten
Titel
Targeting metabolic reprogramming in KRAS-driven cancers
verfasst von
Kenji Kawada
Kosuke Toda
Yoshiharu Sakai
Publikationsdatum
24.06.2017
Verlag
Springer Japan
Erschienen in
International Journal of Clinical Oncology / Ausgabe 4/2017
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-017-1156-4

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