Journal
MOLECULAR MEDICINE REPORTS
Volume 11, Issue 3, Pages 2255-2261Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2014.2904
Keywords
twist-related protein 1; beta-catenin; oral tongue squamous cell carcinoma; cell invasion; matrix metalloproteinase; phosphatidylinositol 3-kinase
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Accumulating evidence suggests that P-catenin signaling may be involved in oral tongue squamous cell carcinoma (OTSCC) cell invasion. Abnormal activation of twist-related protein 1 (TWIST1 or TWIST) has been identified in several types of human cancer. A recent study showed that overexpression of TWIST is associated with a poor prognosis in patients with OTSCC and may enhance OTSCC cell invasion. This study investigated the effect of TWIST on P-catenin signaling in OTSCC cells and its impact on OSTCC cell invasion. Stable overexpression of TWIST, with or without knockdown of P-catenin, and stable knockdown of TWIST were performed in SCC-4 and TCA8113 human OTSCC cells. Overexpression of TWIST in SCC-4 and TCA8113 cells increased beta-catenin signaling luciferase reporter activity, mRNA levels of the beta-catenin signaling target genes, c-Myc and c-Jun levels, soluble beta-catenin level, the phosphorylation status of glycogen synthase kinase-3 beta (GSK-3 beta) at serine 9, matrix metalloproteinase-2 (MMP-2) expression and cell invasion. Knockdown of TWIST had the opposite effect. All of these changes, with the exception of phosphorylation of GSK-3 beta, were eliminated by stable knockdown of beta-catenin. In addition, the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 abrogated the enhancing effects of TWIST on mRNA levels of c-Myc and c-Jun, soluble beta-catenin levels, MMP-2 expression, cell invasion and GSK-313 phosphorylation. In conclusion, the present study demonstrated that TWIST enhances cell invasion and MMP-2 expression in OTSCC cells through beta-catenin signaling, probably via a PI3K-dependent mechanism. This study provides novel insights into the molecular mechanisms underlying OTSCC progression.
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