SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration

Jia-Long Qi; Jin-Rong He; Cun-Bao Liu; Shu-Mei Jin; Xu Yang; Hong-Mei Bai; Yan-Bing Ma

doi:10.1016/j.gendis.2021.03.008

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SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration

更新时间：2022-08-11

- SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration
- Genes & Diseases Vol. 9, Issue 5, (2022)
- 作者机构：
  
  1. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College,Yunnan,Kunming,PR China,530102
  2. Kunming Medical University, Institute of Medical Biology,Yunnan,Kunming,PR China,650500
  3. Yunnan Institute of Materia Medical, Department of Pathology,Yunnan,Kunming,PR China,650111
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2021.03.008
  CLC：
- Published：2022，
  
  Published Online：1 September 2022，
扫描看全文
Jia-Long Qi, Jin-Rong He, Cun-Bao Liu, et al. SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration. [J]. Genes & Diseases 9(5).(2022)
DOI：

Jia-Long Qi, Jin-Rong He, Cun-Bao Liu, et al. SQSTM1/p62 regulate breast cancer progression and metastasis by inducing cell cycle arrest and regulating immune cell infiltration. [J]. Genes & Diseases 9(5).(2022) DOI： 10.1016/j.gendis.2021.03.008.

摘要

Abstract

The autophagy adaptor protein SQSTM1/p62 is overexpressed in breast cancer and has been identified as a metastasis-related protein. However

the mechanism by which SQSTM1/p62 contributes to breast cancer progression and tumor microenvironment remains unclear. This 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/

62 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 vivo

. 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 decreased. RT-PCR analyses showed that the gene expression of Th1/Th2 cytokines changed in the tumor microenvironment. Silencing

SQSTM1

62 suppressed tumor cell lung metastasis. Together

our results provide strong evidence that silencing tumor cell

SQSTM1

62 inhibited tumor growth and metastasis through cell cycle arrest and TME regulation. This finding provides a novel molecular therapeutic strategy for breast cancer progression and metastasis treatment.

关键词

Keywords

Breast cancerCell cycleMetastasisSQSTM1/p62Tumor microenvironment

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