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CLIC4 abrogation promotes epithelial mesenchymal transition in gastric cancer.

CLIC4 has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in… Click to show full abstract

CLIC4 has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by Western blot and RT-PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared to adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells,which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared to N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44, OCT4, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

Keywords: mesenchymal transition; gastric cancer; epithelial mesenchymal; expression; clic4; cancer

Journal Title: Carcinogenesis
Year Published: 2019

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