Xuedan Sun, Lifang He, Hong Liu, Rick Francis Thorne, Taofei Zeng, Liu Liu, Bo Zhang, Miao He, Yabin Huang, Mingyue Li, Enyi Gao, Mengyao Ma, Cheng Cheng, Fanzheng Meng, Chuandong Lang, Hairui Li, Wanxiang Xiong, Shixiang Pan, Delong Ren, Bingyi Dang, Yi Yang, Mian Wu, Lianxin Liu
{"title":"The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.","authors":"Xuedan Sun, Lifang He, Hong Liu, Rick Francis Thorne, Taofei Zeng, Liu Liu, Bo Zhang, Miao He, Yabin Huang, Mingyue Li, Enyi Gao, Mengyao Ma, Cheng Cheng, Fanzheng Meng, Chuandong Lang, Hairui Li, Wanxiang Xiong, Shixiang Pan, Delong Ren, Bingyi Dang, Yi Yang, Mian Wu, Lianxin Liu","doi":"10.1016/j.cmet.2023.07.005","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":null,"pages":null},"PeriodicalIF":27.7000,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2023.07.005","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 1
Abstract
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.
期刊介绍:
Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others.
Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.