Article Publish Status: FREE
Abstract Title:

Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy.

Abstract Source:

Proc Natl Acad Sci U S A. 2013 Jul 23 ;110(30):12331-6. Epub 2013 Jul 8. PMID: 23836662

Abstract Author(s):

Wendy W Hwang-Verslues, Po-Hao Chang, Yung-Ming Jeng, Wen-Hung Kuo, Pei-Hsun Chiang, Yi-Cheng Chang, Tsung-Han Hsieh, Fang-Yi Su, Liu-Chen Lin, Serena Abbondante, Cheng-Yuan Yang, Huan-Ming Hsu, Jyh-Cherng Yu, King-Jen Chang, Jin-Yuh Shew, Eva Y-H P Lee, Wen-Hwa Lee

Article Affiliation:

Wendy W Hwang-Verslues

Abstract:

The circadian clock gene Period2 (PER2) has been suggested to be a tumor suppressor. However, detailed mechanistic evidence has not been provided to support this hypothesis. We found that loss of PER2 enhanced invasion and activated expression of epithelial-mesenchymal transition (EMT) genes including TWIST1, SLUG, and SNAIL. This finding was corroborated by clinical observation that PER2 down-regulation was associated with poor prognosis in breast cancer patients. We further demonstrated that PER2 served as a transcriptional corepressor, which recruited polycomb proteins EZH2 and SUZ12 as well as HDAC2 to octamer transcription factor 1 (OCT1) (POU2F1) binding sites of the TWIST1 and SLUG promoters to repress expression of these EMT genes. Hypoxia, a condition commonly observed in tumors, caused PER2 degradation and disrupted the PER2 repressor complex, leading to activation of EMT gene expression. This result was further supported by clinical data showing a significant negative correlation between hypoxia and PER2. Thus, our findings clearly demonstrate the tumor suppression function of PER2 and elucidate a pathway by which hypoxia promotes EMT via degradation of PER2.

Print Options


This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2024 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.