小柯机器人

中国科学技术大学Lianxin Liu和郑州大学Mian Wu小组合作取得一项新突破。他们发现MC4减少会导致滞育样结直肠癌细胞增殖减慢且对化疗不敏感。2023年8月4日出版的《细胞—代谢》杂志发表了这项成果。

研究人员揭示了SMC4在调控结直肠癌细胞切换到滞育样状态中的多种作用。SMC4减少促进三个糖酵解酶的表达，这会造成乳酸产生增加同时抑制PGAM1。大量的乳酸通过组蛋白乳酸化增加了ABC转运蛋白的表达，使肿瘤细胞对化疗不敏感。SMC4是PGAM1转录的共激活因子，SMC4和PGAM1双缺失会影响F-肌动蛋白组装，导致细胞分裂失败和多倍体产生，从而抑制细胞增殖。

对这些非遗传化疗耐药性机制的了解可能会对该领域产生重大影响，增加人们对肿瘤细胞需氧糖酵解功能的理解，并可能为未来肿瘤的治疗提供启示。

据了解，为了应对不利环境条件，胚胎发育可能会发生可逆地停止，这一过程称为滞育。最近的研究将这种现象与肿瘤对化疗的非遗传反应联系起来，但对其所涉及的机制知之甚少。

附：英文原文

Title: The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity

Author: 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

Issue&Volume: 2023-08-04

Abstract: In response to adverse environmental conditions, embryonic development may reversiblycease, a process termed diapause. Recent reports connect this phenomenon with thenon-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorlyunderstood. Here, we establish a multifarious role for SMC4 in the switching of colorectalcancer cells to a diapause-like state. SMC4 attenuation promotes the expression ofthree investment phase glycolysis enzymes increasing lactate production while alsosuppressing PGAM1. Resultant high lactate levels increase ABC transporter expressionvia histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 actsas co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibitingcell proliferation. These insights into the mechanisms underlying non-genetic chemotherapyresistance may have significant implications for the field, advancing our understandingof aerobic glycolysis functions in tumor and potentially informing future therapeuticstrategies.

DOI: 10.1016/j.cmet.2023.07.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00264-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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