Four and a half LIM domains 2 contributes to the development of human tongue squamous cell carcinoma.

Abstract

Four and a half LIM domains 2 (FHL2) is a protein of 279 amino acids in length containing four full LIM-domains and a half LIM-domain at the amino terminus. FHL2 is one transcriptional cofactor that can interact with many different proteins, such as AP-1, BRCA1, IGFBP, and integrin, and involved in organ differentiation, development, cell apoptosis, and carcinogenesis. Recent studies showed that FHL2 could play different roles acting as co-activator or corepressor in different cancer types, depending on the cell types involved. However, no report about FHL2 function in tongue squamous cell carcinoma (TSCC) is available to date. This study aims to determine the FHL2 expression and its biological functions in TSCC via in vitro and in vivo studies. Results show that FHL2 expression was associated with the pathological differentiation of TSCC samples through immunohistochemistry. FHL2 overexpression could stimulate cell proliferation, invasiveness, and metastases investigated by MTT, flow cytometry, Transwell and cell scratch methods. FHL2 could also elevate tumor-related molecule nuclear transcription factor-B (NF-кB) and β-catenin expression levels both at transcriptional and translational levels through real-time PCR and Western blot analyses. The in vivo nude mice experiment showed that the tumorigenicity of FHL2 overexpression group was significantly increased compared with control groups. These results suggest that FHL2 overexpression could contribute to the growth, proliferation, invasiveness, and metastasis of human tongue squamous cell carcinoma; furthermore, its function in TSCC might be related with the upregulation of NF-кB and β-catenin expressions.