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LASS2主要通过抑制上皮-间质转化(EMT)和促进细胞凋亡来损害胶质瘤干细胞的增殖以及胶质瘤细胞的迁移和侵袭。

LASS2 impairs proliferation of glioma stem cells and migration and invasion of glioma cells mainly via inhibition of EMT and apoptosis promotion.

作者信息

Zhao Wei-Jiang, Fan Yi-Pu, Ou Guan-Yong, Qiao Xin-Yu

机构信息

Cell Biology Department, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, Jiangsu, P.R. China.

Center for Neuroscience, Shantou University Medical College, Shantou 515041, Guangdong, P.R. China.

出版信息

J Cancer. 2022 Apr 18;13(7):2281-2292. doi: 10.7150/jca.71256. eCollection 2022.

DOI:10.7150/jca.71256
PMID:35517425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9066216/
Abstract

LAG1 longevity assurance homolog 2 (LASS2), a highly conserved transmembrane protein, has been reported in several cancer types. However, the roles of LASS2 in glioma biology remain elusive. In the present study, we investigated the expression of LAAS2 in human glioma tissues and the effects of LASS2 on glioma stem cell (GSC) proliferation. Roles of LASS2 in glioma cell migration and invasion were also researched both and . Our results demonstrated that the level of LASS2 is gradually reduced with the increase of glioma grade. The level of LASS2 is significantly lower in GSCs than in non GSCs, whereas overexpression reduced the sphere formation and promoted the differentiation of CD133 glioblastoma cells, as was indicated by reduced levels of CD133 and Nestin. In addition, overexpression significantly reduced colony formation, migration, and invasion of glioma cells by promoting tumor cell apoptosis and inhibiting epithelial-mesenchymal transition (EMT). Overexpression of inhibited U-87 MG cell-derived glioma xenograft growth in nude mice in a manner similar to . Our findings indicate that LASS2 can function as a suppressor of glioma growth, suggesting that modulation of expression may contribute to a novel strategy for the management of glioma via inhibition of GSCs.

摘要

LAG1寿命保证同源物2(LASS2)是一种高度保守的跨膜蛋白,已在多种癌症类型中被报道。然而,LASS2在胶质瘤生物学中的作用仍不清楚。在本研究中,我们调查了LASS2在人胶质瘤组织中的表达以及LASS2对胶质瘤干细胞(GSC)增殖的影响。还研究了LASS2在胶质瘤细胞迁移和侵袭中的作用。我们的结果表明,LASS2水平随着胶质瘤分级的增加而逐渐降低。LASS2在GSCs中的水平明显低于非GSCs,而LASS2过表达减少了球状体形成并促进了CD133胶质母细胞瘤细胞的分化,这表现为CD133和巢蛋白水平降低。此外,LASS2过表达通过促进肿瘤细胞凋亡和抑制上皮-间质转化(EMT),显著减少了胶质瘤细胞的集落形成、迁移和侵袭。LASS2过表达以类似于[未提及的物质]的方式抑制了U-87 MG细胞衍生的胶质瘤异种移植瘤在裸鼠中的生长。我们的研究结果表明,LASS2可作为胶质瘤生长的抑制因子,这表明调节LASS2表达可能有助于通过抑制GSCs来制定一种新的胶质瘤治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/c1dc1fc95daf/jcav13p2281g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/95c82e277681/jcav13p2281g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/34ad6b7a7eb3/jcav13p2281g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/c2842c37696f/jcav13p2281g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/a7a12ebd6805/jcav13p2281g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/c1dc1fc95daf/jcav13p2281g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/95c82e277681/jcav13p2281g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/34ad6b7a7eb3/jcav13p2281g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/c2842c37696f/jcav13p2281g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/a7a12ebd6805/jcav13p2281g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dfb/9066216/c1dc1fc95daf/jcav13p2281g005.jpg

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LASS2 mediates Nrf2-driven progestin resistance in endometrial cancer.LASS2介导子宫内膜癌中Nrf2驱动的孕激素抵抗。
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Rap2B promotes the proliferation and migration of human glioma cells via activation of the ERK pathway.Rap2B通过激活ERK信号通路促进人胶质瘤细胞的增殖和迁移。
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Int J Biol Macromol. 2021 Apr 15;176:145-156. doi: 10.1016/j.ijbiomac.2021.02.043. Epub 2021 Feb 8.
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