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研究揭示激素抑制胃肿瘤发生机制
作者:小柯机器人 发布时间:2020/3/8 14:10:24

美国哥伦比亚大学Timothy C. Wang团队取得一项新突破。他们的研究显示,激素抑制干细胞从而抑制对称细胞分裂和胃肿瘤发生。该项研究成果发表在202035日出版的《细胞-干细胞》上。

他们表示,胃窦的+4干细胞(SC)被Cck2rGPCR)和Delta样配体1DLL1)标记,是一种保留标签的细胞,主要发生不对称细胞分裂。这个+4的窦状SCNotch1/ Numb +,并通过表达胃泌素的内分泌(G)细胞的信号转导而被抑制。胃的化学致癌作用与G细胞丢失、干细胞对称分裂增加、腺体裂变和干细胞谱系追踪更迅速有关,这一过程可以通过外源性胃泌素治疗来抑制。如外显子测序所揭示的,这种激素抑制与胃癌突变负荷的显著降低有关。总之,他们的结果表明胃肿瘤发生与增加对称细胞分裂有关,这有助于突变并被GPCR信号抑制。

研究人员表示,人们认为癌症是由干细胞引起的,但限制突变获得和肿瘤发展的机制尚未得到很好的定义。

附:英文原文

Title: Hormonal Suppression of Stem Cells Inhibits Symmetric Cell Division and Gastric Tumorigenesis

Author: Wenju Chang, Hongshan Wang, Woosook Kim, Yang Liu, Huan Deng, Haibo Liu, Zhengyu Jiang, Zhengchuan Niu, Weiwei Sheng, Osmel Companioni Nápoles, Yihong Sun, Jianmin Xu, Antonia Sepulveda, Yoku Hayakawa, Adam J. Bass, Timothy C. Wang

Issue&Volume: 2020-03-05

Abstract: Cancer is believed to arise from stem cells, but mechanisms that limit the acquisitionof mutations and tumor development have not been well defined. We show that a +4 stemcell (SC) in the gastric antrum, marked by expression of Cck2r (a GPCR) and Delta-like ligand 1 (DLL1), is a label-retaining cell that undergoes predominantasymmetric cell division. This +4 antral SC is Notch1low/ Numb+ and repressed by signaling from gastrin-expressing endocrine (G) cells. Chemicalcarcinogenesis of the stomach is associated with loss of G cells, increased symmetricstem cell division, glandular fission, and more rapid stem cell lineage tracing, aprocess that can be suppressed by exogenous gastrin treatment. This hormonal suppressionis associated with a marked reduction in gastric cancer mutational load, as revealedby exomic sequencing. Taken together, our results show that gastric tumorigenesisis associated with increased symmetric cell division that facilitates mutation andis suppressed by GPCR signaling.

DOI: 10.1016/j.stem.2020.01.020

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30020-5

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx