Twist‑related protein 1 enhances oral tongue squamous cell carcinoma cell invasion through β‑catenin signaling

Zheng,Lian; Li,Ning; Guo,Feng; Jian,Xin‑Chun; Jiang,Can‑Hua; Yin,Ping; Min,An‑Jie; Huang,Long

doi:10.3892/mmr.2014.2904

Twist‑related protein 1 enhances oral tongue squamous cell carcinoma cell invasion through β‑catenin signaling

Authors:
- Lian Zheng
- Ning Li
- Feng Guo
- Xin‑Chun Jian
- Can‑Hua Jiang
- Ping Yin
- An‑Jie Min
- Long Huang
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Affiliations: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: November 7, 2014 https://doi.org/10.3892/mmr.2014.2904
Pages: 2255-2261

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Abstract

Accumulating evidence suggests that β‑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 β‑catenin signaling in OTSCC cells and its impact on OSTCC cell invasion. Stable overexpression of TWIST, with or without knockdown of β‑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 β‑catenin signaling luciferase reporter activity, mRNA levels of the β‑catenin signaling target genes, c‑Myc and c‑Jun levels, soluble β‑catenin level, the phosphorylation status of glycogen synthase kinase‑3β (GSK‑3β) 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‑3β, were eliminated by stable knockdown of β‑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 β‑catenin levels, MMP‑2 expression, cell invasion and GSK‑3β phosphorylation. In conclusion, the present study demonstrated that TWIST enhances cell invasion and MMP‑2 expression in OTSCC cells through β‑catenin signaling, probably via a PI3K‑dependent mechanism. This study provides novel insights into the molecular mechanisms underlying OTSCC progression.

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