title: Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer.
abstract: Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. Furthermore, we identified pivotal roles of GLUD1 and SLC25A13 in nutritional stress. GLUD1 and SLC25A13 were associated with tumor aggressiveness and poorer prognosis of colorectal cancer. In conclusion, GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments.
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyo
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sueda
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Faculty of Mathematics Kyushu University, Fukuoka, 819-0395, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Hugh
authors.initials: H
authors.lastname: Colvin
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Koseki
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Haraguchi
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Cancer Research Institute of Kanazawa University, Kanazawa, Ishikawa, 920-1192, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Gotoh
authors.affiliation: Graduate School of Information Science and Technology, Osaka University, Suita, Osaka, 565-0871.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuda
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Graduate School of Information Science and Technology, Osaka University, Suita, Osaka, 565-0871.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.|Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000231:Adenocarcinoma, Papillary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002952:Citric Acid Cycle / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000172:deficiency; D005969:Glutamate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D055442:Metabolome / Q000235:genetics; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D033681:Mitochondrial Membrane Transport Proteins; C119629:SLC25A13 protein, human; D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005947:Glucose