| Summary: | 博士 === 國立中興大學 === 生物化學研究所 === 99 === Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide; however, accurate molecular markers to predict its prognosis are still limited. In this study, we enrolled 148 OSCC for immunohistochemical (IHC) and clinical analysis. NBS1 overexpression was an independent prognostic marker in
both OSCC and NO-HNSCC cases. In addition, NBS1 overexpression correlated with the phosphorylation levels of Akt and its downstream target mammalian target of rapamycin (mTOR). Previous studies demonstrated that NBS1 activates the EMT regulator snail expression through phosphorylation of Akt. In HNSCC cell lines, overexpression of Snail in the low endogenous Snail/ERCC1 cell lines FaDu increased ERCC1 expression, and hypoxia or overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail- or NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly regulated ERCC1 transcription. Activation of ERCC1 by NBS1-Snail axis is critical in the generation of cisplatin resistance of HNSCC cells. These results not only depicts a novel pathway of chemoresistance but also provides prognostic markers and candidate for therapeutic intervention in HNSCC.
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