Thymosin β4 induces proliferation, invasion, and epithelial-to-mesenchymal transition of oral squamous cell carcinoma.
The epithelial-to-mesenchymal transition (EMT) plays a vital role in carcinogenesis, invasion, and metastasis of many epithelial tumors including oral squamous cell carcinoma (OSCC), a common malignancy of the head and neck. However, the functional role of the actin-sequestering protein thymosin β4 (Tβ4) in the EMT in OSCCs remains unclear. Thus, we investigated whether overexpression of Tβ4 could induce in vitro tumorigenesis such as cell proliferation and anchorage independency and an EMT-like phenotype in OSCCs. Also, we examined whether it affects invasiveness and cell motility-associated signaling molecules. Tβ4-overexpressing OSCCs, SCC-15_Tβ4 and SCC-25_Tβ4, enhanced cell proliferation and colony formation. In addition, we observed that Tβ4 overexpression induced an EMT-like phenotype, accompanied by a decrease in expression of the epithelial cell marker E-cadherin and an increase in expression of mesenchymal cell markers vimentin and N-cadherin. Also, the expression level of Twist1, an EMT-inducing transcription factor, was significantly enhanced in SCC-15_Tβ4 and SCC-25_Tβ4 cells. Tβ4 overexpression augmented in vitro invasion and MMP-2 activity and enhanced the phosphorylation of paxillin and cortactin and expression of LIMK1. Taken together, these results suggest that Tβ4 overexpression could be one of the causes of tumorigenesis and progression in OSCCs. Further investigation on the Tβ4 molecule would encourage the development of specific targets for cancer treatment.
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehakro, Chongro-gu, Seoul, 110-749, Korea.
Kyoung-Ok
KO
Hong
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehakro, Chongro-gu, Seoul, 110-749, Korea.
Jae-Il
JI
Lee
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehakro, Chongro-gu, Seoul, 110-749, Korea.
Sam-Pyo
SP
Hong
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, 101 Daehakro, Chongro-gu, Seoul, 110-749, Korea. hongsd@snu.ac.kr.
Seong-Doo
SD
Hong
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D013947:Thymosin / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000099201:Thymosin beta(4)
D015820:Cadherins; D009687:Nuclear Proteins; D013947:Thymosin; D051879:Twist-Related Protein 1; D014746:Vimentin; D000099201:Thymosin beta(4); C103173:TWIST1 protein, human
Epithelial-to-mesenchymal transition; Invasion; Oral squamous cell carcinoma; Proliferation; Thymosin β4