生物
癌症研究
化疗
结直肠癌
H3K4me3
卵巢癌
癌细胞
细胞生物学
癌症
基因表达
遗传学
基因
发起人
作者
Xuedan Sun,Liu He,Hong Liang,Rick F. Thorne,Taofei Zeng,Liu Liu,Chao Zhang,Miao He,Yu-Ting Huang,Mingyue Li,Ehre Gao,Ming Ma,Cheng Cheng,Fanzheng Meng,Chuandong Lang,Hairui Li,Wei Xiong,S M Pan,Delong Ren,Dang Bingrong,Yi Yang,Mian Wu,Lianxin Liu
出处
期刊:Cell Metabolism
[Elsevier]
日期:2023-09-01
卷期号:35 (9): 1563-1579.e8
被引量:4
标识
DOI:10.1016/j.cmet.2023.07.005
摘要
In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.
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