Twist-related protein 1 enhances oral tongue squamous cell carcinoma cell invasion through beta-catenin signaling.

Accumulating evidence suggests that beta‑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 beta‑catenin signaling in OTSCC cells and its impact on OSTCC cell invasion. Stable overexpression of TWIST, with or without knockdown of beta‑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‑3beta (GSK‑3beta) 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‑3beta, 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‑3beta 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.