Lv Haishu, Zhang Beibei, Weng Xi, Li Youjia, Deng Chaoxian, Wang Rui, Shi Lei, Yin Yuanqin
Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
Department of Pathology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
Breast Cancer (Dove Med Press). 2025 May 28;17:455-470. doi: 10.2147/BCTT.S518760. eCollection 2025.
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.
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.
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.
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.
乳腺癌已成为女性中最常见的恶性肿瘤之一，对公众健康构成重大威胁。作为四跨膜蛋白家族的一员，CD151与肿瘤进展有关，并已被证明可调节驱动恶性肿瘤的各种细胞和分子机制。然而，CD151在三阴性乳腺癌（TNBC）中的具体功能仍不清楚。在本研究中，我们旨在通过关注CD151与整合素α3β1的相互作用来研究其在TNBC中的促肿瘤作用，整合素α3β1常与CD151形成复合物。
我们的研究首先通过免疫组织化学和蛋白质印迹分析评估TNBC患者临床样本和TNBC细胞系中CD151的表达。通过RNA干扰（RNAi）和构建过表达质粒，我们进一步验证了CD151对TNBC细胞迁移和侵袭的影响。然后通过单细胞RNA测序筛选差异表达基因，并对这些基因进行富集和分析。免疫共沉淀研究证明了CD151与整合素α3β1的结合。蛋白质印迹分析用于评估与上皮-间质转化（EMT）和丝裂原活化蛋白激酶（MAPK）信号通路相关的蛋白质表达。
CD151在TNBC组织和细胞系中高表达。它通过促进EMT增强了TNBC细胞的迁移和侵袭能力。免疫共沉淀证明了CD151与整合素α3β1的结合。此外，我们发现敲低整合素α3β1或CD151均可降低TNBC细胞在体外的迁移和侵袭。蛋白质印迹分析显示，CD151-整合素α3β1复合物可激活TNBC细胞中的MAPK信号通路，随后导致这些细胞发生EMT。
基于我们的研究结果，我们提出了一种新的机制，即CD151通过启动EMT介导肿瘤进展。这表明CD151可被视为TNBC的潜在治疗靶点。
