Key result
LASP-1 protein expression was significantly upregulated in primary oral squamous cell carcinomas compared to normal oral tissues, and its knockdown inhibited tumor growth by arresting cell-cycle progression at the G2 phase.
Why the study?
Does LASP-1 knockdown reduce cellular proliferation and tumor growth in oral squamous cell carcinoma models?
Does LASP-1 knockdown reduce cellular proliferation and tumor growth in oral squamous cell carcinoma models?
Absolute Event Rate: 178% vs 35%
p-value: p=<0.001
Overexpression of LASP-1 is linked to oral tumorigenicity, and its knockdown inhibits tumor cellular growth by mediating G2/M transition.
Hypothesis-generating for LASP-1 targeting in oral cancer models; human trials needed before clinical consideration.
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.
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Shimizu et al. (2013) studied Oral squamous cell carcinoma (n=50). LASP-1 overexpression vs. Normal oral tissues was evaluated on LASP-1 protein expression (IHC score) (p=<0.001). LASP-1 protein expression was significantly upregulated in primary oral squamous cell carcinomas compared to normal oral tissues, and its knockdown inhibited tumor growth by arresting cell-cycle progression at the G2 phase.
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