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Biomarkers, genomics, proteomics, and gene regulation
Concomitant Induction of Apoptosis and Autophagy by Prostate Apoptosis Response-4 in Hypopharyngeal Carcinoma Cells

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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.

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Supported by the Taiwan National Science Council grant NSC99-2320-B-320-014-MY2 and the Taiwan Department of Health grant DOH97-TD-I-111-TM017.