CD151 Promotes Cancer Progression in Triple-Negative Breast Cancer by Inducing EMT through the MAPK Signaling Pathway.

BACKGROUND

Breast cancer has become one of the most prevalent malignant neoplasms among women, poses a significant threat to public health. As a member of the tetraspanin family of proteins, CD151 is implicated in tumor progression and has been shown to regulate various cellular and molecular mechanisms that drive malignancy. However, the specific functions of CD151 in triple-negative breast cancer (TNBC) remain unclear. In this study, we aimed to investigate the pro-tumorigenic role of CD151 in TNBC by focusing on its interaction with integrin α3β1, which often forms a complex with CD151.

METHODS

Our study first evaluated CD151 expression in clinical samples from TNBC patients and TNBC cell lines by immunohistochemistry and Western blotting analysis. Through RNA interference (RNAi) and constructed overexpressed plasmids, we further validated the impact of CD151 on the migration and invasion of TNBC cells. Then the differentially expressed genes were screened by single-cell RNA sequencing, and these genes were enriched and analyzed. Co-immunoprecipitation studies demonstrated the binding of CD151 with integrin α3β1. Western blotting analysis was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT) and Mitogen-activated protein kinase (MAPK) signaling pathway.

RESULTS

CD151 is highly expressed in TNBC tissues and cell lines. It enhanced the migration and invasive ability of TNBC cells by promoting EMT. Co-IP demonstrated the binding of CD151 and integrin α3β1. In addition, we found that knockdown of either integrin α3β1 or CD151 reduced the migration and invasion of TNBC cells in vitro. Western blot analysis revealed that the CD151-integrin α3β1 complex could activate the MAPK signaling pathway in TNBC cells, subsequently leading to EMT of these cells.

CONCLUSION

Based on our findings, we propose a novel mechanism by which CD151 mediates tumor progression through the initiation of EMT. This suggests that CD151 could be considered a potential therapeutic target for TNBC.