SQSTM1/p62 Regulate Breast Cancer Progression and Metastasis by Inducing Cell Cycle Arrest and Regulating Immune Cell Infiltration

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 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 expression significantly inhibited cell proliferation, migration, and invasion, and promoted cell death , 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 CD4IFN-γ (Th1) cells were increased while those of CD4IL-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 /62 suppressed tumor cell lung metastasis. Together, our results provide strong evidence that silencing tumor cell /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.