Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells

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• 作者：A.C. Torres-Martí ; nez ; J.F. Gallardo-Vera ; A.N. Lara-Holguin ; L.F. Montañ ; o ; E.P. Rendó ; n-Huerta ; ^{erendon@unam.mx}
• 关键词：Claudin ; MMP-2 ; Cldn-6 ; Cldn-1 ; MMP-14
• 刊名：Experimental Cell Research
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：350
• 期：1
• 页码：226-235
• 全文大小：2777 K
• 卷排序：350

文摘

Claudins participate in tissue barrier function. The loss of this barrier is associated to metalloproteases-related extracellular matrix and basal membranes degradation. Claudin-1 is a pro-MMP-2 activator and claudin-6 transfected AGS (AGS-Cld6) cells are highly invasive. Our aim was to determine if claudin-6 was direct or indirectly associated with MMP-2 activation and cell invasiveness. Cytofluorometry, cell fractioning, immunoprecipitation, gelatin-zymography, cell migration and invasiveness assays were performed, claudin-2, -6, -7 and -9 transfected AGS cells, anti-MMP-2, -9 and -14, anti-claudins specific antibodies and claudin-1 small interfering RNA were used. The results showed a significant (p<0.001) overexpression of claudin-1 in AGS-Cld6 cell membranes. A strong MMP-2 activity was identified in culture supernatants of AGS-Cld6. Claudin-1 co-localized with MMP-2 and MMP-14; interestingly a significant increase in cell membrane and cytosol MMP-14 expression was detected in AGS-Cld6 cells (p<0.05). Silencing of claudin-1 in AGS-Cld6 cells showed a 60% MMP-2 activity decrease in culture supernatants and a significant decrease (p<0.05) in cell migration and invasiveness. Our results suggest that claudin-6 induces MMP-2 activation through claudin-1 membrane expression, which in turn promotes cell migration and invasiveness.