Genome-wide CRISPR screen identifies ESPL1 limits the response of gastric cancer cells to apatinib

作者全名："Zhang, Bei; Chen, Yan; Chen, Xinqi; Ren, Zhiyao; Xiang, Hong; Mao, Lipeng; Zhu, Guodong"

作者地址："[Zhang, Bei; Ren, Zhiyao; Zhu, Guodong] Guangzhou Med Univ, Guangzhou Geriatr Hosp, Inst Gerontol, Guangzhou, Peoples R China; [Zhang, Bei; Ren, Zhiyao; Zhu, Guodong] Guangzhou Med Univ, Guangzhou Geriatr Hosp, State Key Lab Resp Dis, Guangzhou, Peoples R China; [Zhang, Bei; Ren, Zhiyao; Zhu, Guodong] Collaborat Innovat Ctr Civil Affairs Guangzhou, Guangzhou, Peoples R China; [Chen, Yan] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing, Peoples R China; [Chen, Xinqi] Southern Med Univ, Affiliated Dongguan Hosp, Dept Oncol, Dongguan, Peoples R China; [Xiang, Hong] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Oncol, Guangzhou, Peoples R China; [Mao, Lipeng] Jinan Univ, Sch Med, Dept Syst Biomed Sci, Guangzhou, Peoples R China"

通信作者："Zhu, GD (通讯作者)，Guangzhou Med Univ, Guangzhou Geriatr Hosp, Inst Gerontol, Guangzhou, Peoples R China.; Zhu, GD (通讯作者)，Guangzhou Med Univ, Guangzhou Geriatr Hosp, State Key Lab Resp Dis, Guangzhou, Peoples R China.; Zhu, GD (通讯作者)，Collaborat Innovat Ctr Civil Affairs Guangzhou, Guangzhou, Peoples R China."

来源：CANCER CELL INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001172827500003

JCR分区：Q1

影响因子：5.3

年份：2024

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Apatinib resistance; ESPL1; CRISPR screening; MDM2; Gastric cancer

摘要："Apatinib was the first anti-angiogenic agent approved for treatment of metastatic gastric cancer (GC). However, the emergence of resistance was inevitable. Thus investigating new and valuable off-target effect of apatinib directly against cancer cells is of great significance. Here, we identified extra spindle pole bodies-like 1 (ESPL1) was responsible for apatinib resistance in GC cells through CRISPR genome-wide gain-of-function screening. Loss of function studies further showed that ESPL1 inhibition suppressed cell proliferation, migration and promoted apoptosis in vitro, and accordingly ESPL1 knockdown sensitized GC cells to apatinib. In addition, we found ESPL1 interacted with mouse double minute 2 (MDM2), a E3 ubiquitin protein ligase, and the combination of MDM2 siRNA with apatinib synergistically ameliorated the resistance induced by ESPL1 overexpression. In summary, our study indicated that ESPL1 played a critical role in apatinib resistance in GC cells. Inhibition of MDM2 could rescue the sensitivity of GC cells to apatinib and reverse ESPL1-mediated resistance."

基金机构：Guangdong Basic and Applied Basic Research Foundation

基金资助正文：No Statement Available