A Positive Tetraspanin 8 (TSPAN8)/β-Catenin Regulatory Loop Enhances the Stemness of Colorectal Cancer Cells.

BACKGROUND The expression of (tetraspanin 8) is upregulated in colorectal cancer; however, its roles in colorectal cancer progression are never been revealed. This work aimed to investigate Tduanyu1842N8 effects and the molecular basis in regulating colorectal cancer stemness. MATERIAL AND METHODS Real-time quantitative polymerase chain reaction and western blot analysis were used to detect the expression of Tduanyu1842N8 expression in clinical samples and the expression of stemness genes in colorectal cancer cells. Sphere forming analysis was performed to detect Tduanyu1842N8 effects on sphere forming ability of colorectal cancer cells. Co-IP and ChIP analysis were performed to confirm the molecular basis contributing to effects on colorectal cancer stemness. RESULTS Tduanyu1842N8 expression is increased in colorectal cancer tissues. Knockdown of Tduanyu1842N8 reduced the expression of stemness genes and sphere forming capacity in colorectal cancer cells. Mechanistically, Tduanyu1842N8 directly interacted ß-catenin and enhanced its protein expression, which is necessary for Tduanyu1842N8-mediated effects on colorectal cancer stemness. Conversely, ß-catenin directly bound to Tduanyu1842N8 promoter and enhanced Tduanyu1842N8 transcription. CONCLUSIONS Tduanyu1842N8 promotes colorectal cancer stemness through a positive regulatory loop.

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