Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer

Masaaki Miyo, Masamitsu Konno, Naohiro Nishida, Toshinori Sueda, Kozo Noguchi, Hidetoshi Matsui, Hugh Colvin, Koichi Kawamoto, Jun Koseki, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Noriko Gotoh, Fumio Matsuda, Taroh Satoh, Tsunekazu Mizushima, Hiroshi Shimizu, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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.

Original languageEnglish
Article number38415
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Dec 7 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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