瓦博格效应
化学
mTORC1型
mTORC2型
生物
碳水化合物代谢
安普克
细胞生物学
作者
Meilin Weng,Wankun Chen,Xiangyuan Chen,Hong Lu,Zhirong Sun,Qi Yu,Pengfei Sun,Yajun Xu,Minmin Zhu,Nan Jiang,Jin Zhang,Jian-ping Zhang,Yuanlin Song,Duan Ma,Xiao-ping Zhang,Changhong Miao
标识
DOI:10.1038/s41467-020-15795-8
摘要
Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis. The molecular mechanisms underpinning how fasting inhibits tumourigenesis are not completely elucidated. Here, the authors show that fasting upregulates the cholesterogenic gene FDFT1 which leads to decreased AKT/mTOR/HIF1a signalling and glycolysis reduction in colorectal cancer.
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