Twist-related protein 1 enhances oral tongue squamous cell carcinoma cell invasion through β-catenin signaling.
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.
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Lian
L
Zheng
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Ning
N
Li
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Feng
F
Guo
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Xin-Chun
XC
Jian
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Can-Hua
CH
Jiang
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Ping
P
Yin
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
An-Jie
AJ
Min
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Long
L
Huang
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D020778:Matrix Metalloproteinase 2