RRC ID 44833
著者 Shimizu F, Shiiba M, Ogawara K, Kimura R, Minakawa Y, Baba T, Yokota S, Nakashima D, Higo M, Kasamatsu A, Sakamoto Y, Tanzawa H, Uzawa K.
タイトル Overexpression of LIM and SH3 Protein 1 leading to accelerated G2/M phase transition contributes to enhanced tumourigenesis in oral cancer.
ジャーナル PLoS One
Abstract BACKGROUND:LIM 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.
METHODS:We 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.
RESULTS:Significant 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.
CONCLUSION:Our 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.
巻・号 8(12)
ページ e83187
公開日 2013-1-1
DOI 10.1371/journal.pone.0083187
PII PONE-D-13-34583
PMID 24386158
PMC PMC3873298
MeSH Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Carcinogenesis / genetics Cell Division / genetics Cell Line, Tumor Cell Proliferation Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / metabolism G2 Phase / genetics G2 Phase Cell Cycle Checkpoints / genetics Gene Knockdown Techniques Humans LIM Domain Proteins / genetics* LIM Domain Proteins / metabolism Mouth Neoplasms / genetics* Mouth Neoplasms / pathology RNA, Messenger / metabolism Up-Regulation
IF 2.74
引用数 28
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Sa3(RCB0980) HO-1-u-1(RCB2102) HSC-4(RCB1902) Ca9-22(RCB1976)