Overexpression of LIM and SH3 Protein 1 Leading to Accelerated G2/M Phase Transition Contributes to Enhanced Tumourigenesis in Oral Cancer |
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Authors: | Fumie Shimizu Masashi Shiiba Katsunori Ogawara Ryota Kimura Yasuyuki Minakawa Takao Baba Satoshi Yokota Dai Nakashima Morihiro Higo Atsushi Kasamatsu Yosuke Sakamoto Hideki Tanzawa Katsuhiro Uzawa |
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Institution: | 1. Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.; 2. Department of Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.; 3. Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.; Deutsches Krebsforschungszentrum, Germany, |
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Abstract: | BackgroundLIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein involved in several malignant tumors. However, its role in oral squamous cell carcinoma (OSCC) is unknown. The aim of this study was to characterize the role and molecular status/mechanism of LASP-1 in OSCC.MethodsWe evaluated LASP-1 mRNA and protein expressions in OSCC-derived cell lines and primary OSCCs. Using an shRNA system, we analyzed the effect of LASP-1 on the biology and function of the OSCC cell lines, HSC-3 and Ca9-22. The cells also were subcutaneously injected to evaluate tumor growth in vivo. Data were analyzed by the Fisher’s exact test or the Mann-Whitney U test. Bonferroni correction was used for multiple testing.ResultsSignificant up-regulation of LASP-1 was detected in OSCC-derived cell lines (n = 7, P<0.007) and primary OSCCs (n = 50, P<0.001) compared to normal controls. LASP-1 knockdown cells significantly inhibited cellular proliferation compared with shMock-transfected cells (P<0.025) by arresting cell-cycle progression at the G2 phase. We observed dramatic reduction in the growth of shLASP-1 OSCC xenografts compared with shMock xenografts in vivo.ConclusionOur results suggested that overexpression of LASP-1 is linked closely to oral tumourigenicity and further provide novel evidence that LASP-1 plays an essential role in tumor cellular growth by mediating G2/M transition. |
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