气候变化领域集成服务门户(CCPortal): Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin

CCPortal

DOI	10.1073/pnas.2020478118
	Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin
	Wijshake T.; Zou Z.; Chen B.; Zhong L.; Xiao G.; Xie Y.; Doench J.G.; Bennett L.; Levine B.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown. To address this question, we performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reverse Beclin 1-dependent inhibition of cellular proliferation. Small guide RNAs targeting CDH1 and CTNNA1, tumor-suppressor genes that encode cadherin/catenin complex members E-cadherin and alpha-catenin, respectively, were highly enriched in the screen. CRISPR/Cas9-mediated knockout of CDH1 or CTNNA1 reversed Beclin 1-dependent suppression of breast cancer cell proliferation and anchorage-independent growth. Moreover, deletion of CDH1 or CTNNA1 inhibited the tumor-suppressor effects of Beclin 1 in breast cancer xenografts. Enforced Beclin 1 expression in MCF7 cells and tumor xenografts increased cell surface localization of E-cadherin and decreased expression of mesenchymal markers and beta-catenin/Wnt target genes. Furthermore, CRISPR/Cas9-mediated knockout of BECN1 and the autophagy class III phosphatidylinositol kinase complex 2 (PI3KC3-C2) gene, UVRAG, but not PI3KC3-C1–specific ATG14 or other autophagy genes ATG13, ATG5, or ATG7, resulted in decreased E-cadherin plasma membrane and increased cytoplasmic E-cadherin localization. Taken together, these data reveal previously unrecognized cooperation between Beclin 1 and E-cadherin–mediated tumor suppression in breast cancer cells. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Beclin 1; Breast cancer; E-cadherin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180793
作者单位	Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States; Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
推荐引用方式 GB/T 7714	Wijshake T.,Zou Z.,Chen B.,et al. Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin[J],2021,118(5).
APA	Wijshake T..,Zou Z..,Chen B..,Zhong L..,Xiao G..,...&Levine B..(2021).Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Wijshake T.,et al."Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).