Reference - Detail
| RRC ID | 64636 |
|---|---|
| Author | Miyo M, Konno M, Nishida N, Sueda T, Noguchi K, Matsui H, Colvin H, Kawamoto K, Koseki J, Haraguchi N, Nishimura J, Hata T, Gotoh N, Matsuda F, Satoh T, Mizushima T, Shimizu H, Doki Y, Mori M, Ishii H. |
| Title | Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer. |
| Journal | Sci Rep |
| 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. |
| Volume | 6 |
| Pages | 38415 |
| Published | 2016-12-7 |
| DOI | 10.1038/srep38415 |
| PII | srep38415 |
| PMID | 27924922 |
| PMC | PMC5141444 |
| MeSH | Adaptation, Physiological / genetics Adenocarcinoma, Mucinous / diagnosis Adenocarcinoma, Mucinous / genetics* Adenocarcinoma, Mucinous / metabolism Adenocarcinoma, Mucinous / mortality Adenocarcinoma, Papillary / diagnosis Adenocarcinoma, Papillary / genetics* Adenocarcinoma, Papillary / metabolism Adenocarcinoma, Papillary / mortality Aged Biomarkers, Tumor / genetics* Biomarkers, Tumor / metabolism Cell Line, Tumor Cell Proliferation Cell Survival Citric Acid Cycle / genetics Colorectal Neoplasms / diagnosis Colorectal Neoplasms / genetics* Colorectal Neoplasms / metabolism Colorectal Neoplasms / mortality Female Gene Expression Glucose / deficiency Glutamate Dehydrogenase / genetics* Glutamate Dehydrogenase / metabolism Humans Lymphatic Metastasis Male Metabolome / genetics Middle Aged Mitochondrial Membrane Transport Proteins / genetics* Mitochondrial Membrane Transport Proteins / metabolism Prognosis Proto-Oncogene Proteins p21(ras) / genetics Proto-Oncogene Proteins p21(ras) / metabolism Stress, Physiological / genetics Survival Analysis |
| IF | 3.998 |
| Resource | |
| Human and Animal Cells | NIH3T3 |