The tumor-suppressive activity of prostate apoptosis response-4 (Par-4) has been demonstrated in a variety of human cancers. In this study, for the first time to our knowledge, we demonstrated that a higher intensity of Par-4 was significantly correlated with a better response in patients with hypopharyngeal carcinoma undergoing radiotherapy alone or concurrent chemoradiotherapy. Mechanistically, an elevated expression of Par-4 induced apoptosis of hypopharyngeal carcinoma cells and sensitized cells toward chemotherapeutic agents or X-ray irradiation. Along with apoptotic incitation, intriguingly, autophagic flux also increased on Par-4 stimulation and contributed to cell death. Moreover, the expressions of multiple common regulators involved in apoptosis and autophagy were regulated by Par-4. Taken together, our results suggested a prognostic role of Par-4 in hypopharyngeal carcinoma and showed novel activity of Par-4 in apoptosis and autophagy induction. © 2014 American Society for Investigative Pathology.
Wang, L. J., Chen, P. R., Hsu, L. P., Hsu, W. L., Liu, D. W., Chang, C. H., … Lee, J. W. (2014). Concomitant induction of apoptosis and autophagy by prostate apoptosis response-4 in hypopharyngeal carcinoma cells. American Journal of Pathology, 184(2), 418–430. https://doi.org/10.1016/j.ajpath.2013.10.012