SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration
作者机构：Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingYunnan 530102PR China Kunming Medical UniversityInstitute of Medical BiologyKunmingYunnan 650500PR China Yunnan Institute of Materia MedicalDepartment of PathologyKunmingYunnan 650111PR China
出 版 物：《Genes & Diseases》 (基因与疾病（英文）)
年 卷 期：2022年第9卷第5期
页 面：1332-1344页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071007[理学-遗传学] 0703[理学-化学]
基 金：supported by the CAMS Initiative for Innovative Medicine(No.2016-I2M-1-019) 2017-I2M-3-022,the Fundamental Research Funds for the Central Universities of China(No.3332019162) the funds for IMBCAMS PhD Innovation(No.2018018001) the Foundation for Studying Abroad from the China Scholarship Council(No.201808110121,201906210477)
主 题：Breast cancer Cell cycle Metastasis SQSTM1/p62 Tumor microenvironment
摘 要：The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related ***,the mechanism by which SQSTM1/p62 contributes to breast cancer progression and tumor microenvironment remains *** study revealed that silencing SQSTM1/p62 expression suppressed breast cancer progression via regulating cell proliferation and reshaping the tumor microenvironment(TME).Here,we found that SQSTM1/p62 was overexpressed in multiple human cancer tissue types and that was correlated with poor patient overall survival(OS)and disease-free survival(DFS).Moreover,we found that short-hairpin RNA(shRNA)-mediated knockdown of p62 expression significantly inhibited cell proliferation,migration,and invasion,and promoted cell death in vitro,as well as suppressed breast cancer growth and lung metastasis in *** addition,flow cytometry analysis of splenocytes and tumor infiltrating lymphocytes(TILs)indicated that the numbers of CD8α+interferon(IFN)-γ+cells(CTLs)and CD4+IFN-γ+(Th1)cells were increased while those of CD4+IL-4+(Th2)cells,tumor-associated macrophages(TAMs)and myeloid-derived suppressor cells(MDSCs)were ***-PCR analyses showed that the gene expression of Th1/Th2 cytokines changed in the tumor *** SQSTM1/p62 suppressed tumor cell lung ***,our results provide strong evidence that silencing tumor cell SQSTM1/p62 inhibited tumor growth and metastasis through cell cycle arrest and TME *** finding provides a novel molecular therapeutic strategy for breast cancer progression and metastasis treatment.
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