Exocyst complex component Sec8: a presumed component in the progression of human oral squamous-cell carcinoma by secretion of matrix metalloproteinases

胞吐复合体成分Sec8:被认为是通过分泌基质金属蛋白酶参与人类口腔鳞状细胞癌进展的成分

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Abstract

PURPOSE: Sec8, a component of the exocyst complex, has been implicated in tethering of secretory vesicles to specific regions on the plasma membrane. To investigate the involvement of Sec8 in oral squamous-cell carcinoma (OSCC), we evaluated the expression status and effect of Sec8 in OSCC cell lines. METHODS: Sec8 mRNA and protein expressions in human OSCC cell lines were assessed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting. Functional analyses, proliferation assay, invasiveness assay, and gelatin zymography in Sec8 knockdown cells were performed. Also the correlation between Sec8 expression and the clinicopathological features in 98 primary OSCCs samples was evaluated by immunohistochemistry. RESULTS: Sec8 mRNA and protein expression were significantly up-regulated in all cell lines (p < 0.05). Sec8 knockdown cells were characterized by reduced cellular proliferation, invasiveness, and secretion of matrix metalloproteinases (MMPs) (MMP-2, proMMP-2, and proMMP-9). Sec8 protein expression in primary OSCCs also was significantly (p < 0.05) greater than in normal counterparts, and higher Sec8 expression was correlated with tumor size (p = 0.03). CONCLUSIONS: Our results suggested for the first time that Sec8 might play a specific role in OSCC progression by mediating MMP secretion.

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