Role of ß-catenin in cisplatin resistance, relapse and prognosis of head and neck squamous cell carcinoma.

ABSTRACT

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer in India with high incidence and rapid recurrence rates. Here, we aimed to investigate the role of ß-catenin, a developmental pathway gene, in HNSCC therapy resistance, DNA damage response, recurrence and prognosis. METHODS: In total 80 HNSCC samples were included. Western blot, immunohistochemistry and qRT-PCR analyses were performed to assess ß-catenin expression in the cut margin and tumor areas of each sample. Kaplan-Meier analyses were performed to correlate ß-catenin expression with the survival and prognosis of HNSCC patients. In addition, chemo-resistance, DNA damage response and DNA repair capacities were evaluated in HNSCC-derived cell lines through LiCl-mediated up-regulation and siRNA-mediated silencing of ß-catenin expression. RESULTS: We observed ß-catenin up-regulation in cut margin areas of recurrent patients compared to their corresponding tumor regions, which subsequently could be associated with poor prognosis. In addition, we found that LiCl-mediated up-regulation of ß-catenin in HNSCC-derived cells led to cisplatin resistance, evasion of apoptosis, enhanced DNA repair and enhanced migration. The effects of ß-catenin silencing correlated with its putative role in chemo-resistance and DNA damage response. CONCLUSION: From our results we conclude that ß-catenin may contribute to HNSCC therapy resistance and disease relapse. As such, ß-catenin may be explored as a therapeutic target along with conventional therapeutics.