The mechanisms underlying repression of glycolysis by detachment and its significance in detachment-induced cell death

Research Project

Project/Area Number	25860247
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Pathological medical chemistry
Research Institution	Showa University
Principal Investigator	ISHIKAWA FUMIHIRO 昭和大学, 薬学部, 助教 (60515667)
Project Period (FY)	2013-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	がん / 足場依存的生存 / 代謝 / DICD / アノイキス
Outline of Final Research Achievements	In this study, we investigated the relationship between detachment-induced cell death (DICD) and changes in glucose metabolism for a better understanding of resistance to DICD acquired by metastatic cancer cells. First, we observed the accumulation of fructose-6-phosphate (F6P) in normal human mammary epithelial cells during DICD. Because F6P is a metabolic intermediate in both glycolysis and the hexamine pathways and detachment scarcely suppressed glycolysis, it was assumed that the hexamine pathway was suppressed in response to detachment, which resulted in DICD. To examine whether inhibition of the hexamine pathway is sufficient to induce cell death, we used the inhibitor of the rate-limiting enzyme, azaserine, in the hexamine pathway. Treatment with azaserine remarkably evoked cell death even under adherent condition. Thus, it was suggested that DICD may be mediated by repression of the hexamine pathway.