CD151 promotes breast cancer metastasis by activating TGF-β1/Smad signaling pathway

S.-J. Zhao, H.-D. Zhao, J. Li, H. Zhang, D.-T. Gao, Q. Wang

Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, China. z.hddl@outlook.com

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• Oncology

OBJECTIVE: This study aimed to explore the expression characteristics of CD151 in breast cancer (BC) and to further study its role in the development of BC and potential regulatory mechanisms.

PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was used to detect the level of CD151 in 82 pairs of BC tissues and adjacent normal ones, and the relationship between CD151 expression and BC pathological parameters and prognosis was analyzed. CD151 expression in BC cells was further validated using qRT-PCR. The CD151 knockdown model was constructed in BC cell lines including MCF-7 and SKBR3 using the small interference RNA. The cell counting kit-8 (CCK-8) and transwell assay were used to analyze the effect of CD151 on the biological function of BC cells, and finally Western blot was performed to explore its underlying mechanism.

RESULTS: QRT-PCR analysis revealed that CD151 level in BC tissues was strikingly higher than that in normal ones, and the difference was statistically significant. Compared with patients with low CD151 level, patients with high CD151 level had worse tumor stage, lymph node metastasis, and distant metastases. The higher the incidence of metastasis, the lower the overall survival rate. Compared with the negative control group, the ability of cell proliferation or invasion and migration in the CD151 knockdown group was significantly reduced. In addition, Western blot results demonstrated that the levels of proteins in TGF-β1/Smad pathway, including transforming growth factor-β1 (TGF-β1), p-Smad2, p-Smad3, N-cad, Vimentin and MMP-9, were remarkably decreased in cells of si-CD151 group.

CONCLUSIONS: The expression of CD151 in BC was significantly increased, which was found evidently associated with BC stage, lymph node or distant metastasis, and poor prognosis. Meanwhile, CD151 may promote the proliferation and invasion of BC by regulating TGF-β1/Smad pathway.

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