Secretory Kin17 is Correlated with Chemoresistance in Oral Squamous Cell Carcinoma

 Purpose: Kin17 is a conserved nuclear protein that participates in DNA damage repair, DNA replication and cell proliferation. Several reports have linked Kin17 to tumor progression. However, the role of Kin17 in oral squamous cell carcinoma (OSCC) has not yet been described. The aims of this study were to assess Kin17 transcript and protein expression in OSCC and to evaluate an association for this protein with chemoresistance. Methods: Kin17 expression in OSCC tissues and OSCC cell lines was measured by standardized immunohistochemistry, western blotting and semi-quantitative RT-PCR. Secretory Kin17 protein was measured in serum samples and cell culture conditioned media. A recombinant Kin17 protein was purified and used in a chemoresistance assay. Results: Kin17 was identified as an unconventional secretory protein, whose expression levels were correlated with chemotherapy and chemoresistance in OSCC. Kin17 protein expression was up-regulated in patients exhibiting chemoresistance. Serum Kin17 levels were significantly increased in patients receiving chemotherapy. We provide evidence that the secretory Kin17 protein plays a role in the DNA damage response in OSCC. Furthermore, we also show that the secretory Kin17 protein enhances the chemoresistance of OSCC cells and increases the expression of multidrug resistant genes. Conclusion:To our knowledge, this is the first report of Kin17 being characterized as a secretory protein. This novel role for Kin17 may have implications for studying the chemoresistance process in OSCC. The effective inhibition of Kin17 secretion may improve or prolong chemotherapeutic effects, making it an attractive therapeutic target candidate for further study.