mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells. (Cancer Cell 2016, 29:548-562.)

報告日期: 2017/03/10
報告時間: 5:10/6:00
報告學生: 李婉寧(以英文報告)
講評老師: 彭怡禎
附件下載: 下載[1638-1487732364-1.pdf] 

mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells

Pusapati RV et al. Cancer Cell. 2016 Apr 11;29(4):548-62. doi: 10.1016/j.ccell.2016.02.018.

Speaker: Wan-Ning Li(李婉寧)Mar. 10th, 2017

Commentator: Peng, I-Chen(彭怡禎)老師

Abstract

It has been reported that glycolysis is elevated in many kinds of cancer cells for decades. However, the therapeutic strategy of targeting glycolysis alone to reduce the tumor size seems to be ineffective. Hence, there may be alternate metabolic pathways participating in tumor growth to maintain the survival of proliferating cells and to produce the biomass they need. The author has demonstrated that active mTORC1 signaling pathway, a key regulator of cellular energy and biomass production, is able to help the cells circumventing the glycolysis disruption. Once the glycolysis is blocked, mTORC1 controls the increased glucose flux into the pentose phosphate pathway and then directs them back into glycolysis again. Consequently, the cells can still generate their energy and essential factors to sustain the living under disrupted glycolysis. On the other hand, the cells also benefit from the NADPH. The higher production of NADPH from oxidative PPP provides reducing power against ROS levels in the cells which may explain the relatively high OXPHOS rates in GI cells. Through the strong evidence shown, it may be a possible way to reduce the tumor growth by using combinatorial therapeutic strategies to co-inhibit glycolysis and mTORC1 signaling.