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학술저널
저자정보
박현식 (을지대학교) 이수혁 (을지대학교) 이지수 (을지대학교) 신현빈 (을지대학교) 유승민 (을지대학교) 이명신 (을지대학교) 박진성 (을지대학교)
저널정보
대한비뇨기과학회 Investigative and Clinical Urology Investigative and Clinical Urology Vol.60 No.5
발행연도
2019.1
수록면
396 - 404 (9page)

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Purpose: CD81 is a prognostic biomarker for high-grade bladder cancer (BC). In this study, we aimed to determine the functional mechanisms underlying the role of CD81 in BC progression. Materials and Methods: In two invasive BC cell lines (T24, J82), CD81 expression was suppressed by the transfection of lentiviral vectors including CD81-specific shRNAs, and then the migration and invasion of BC cells was analyzed. Enzymatic activity of matrix metalloproteinases (MMPs) was also analyzed by collagen-zymography. The expression of MMPs was confirmed by western blotting using culture supernatants from each cell line. Signaling pathways related to MMPs were investigated using various antibodies. Results: CD81 was successfully knocked down by shRNAs in T24 and J82 cell lines. While the migration of BC cells was not affected after the knockdown of CD81, the invasive activity was significantly increased in both cell lines. Zymography produced distinct bands using supernatants from CD81-knockdown cells, whereas only faint bands were observed with empty vector-transfected cells. We also observed an increased expression of MMPs, specifically MMP2 and 9, in the conditioned media from CD81-knockdown cells by western blotting. Mechanistically, the phosphorylation of extracellular signal-regulated kinase (ERK) was associated with the invasive activity of BC cells, while U0126 (an ERK inhibitor) reduced the invasive activity of CD81-knockdown BC cells. Conclusions: Taken together, CD81 suppression promotes the invasive property of BC cells through MMP signaling via ERK phosphorylation. Our results suggest that the regulation of CD81 expression may have some therapeutic potential in BC.

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