Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells.

Abstract

BACKGROUND & AIMS Aberrant activation of the signal transducer and activator of transcription (Stat)3 and overexpression of polo-like kinase (PLK)1 each have been associated with cancer pathogenesis. The mechanisms and significance of dysregulation of Stat3 and PLK1 in carcinogenesis and cancer progression are unclear. We investigated the relationship between Stat3 and PLK1 and the effects of their dysregulation in esophageal squamous cell carcinoma (ESCC) cells. METHODS We used immunoblot, quantitative reverse-transcription polymerase chain reaction, immunochemistry, chromatin immunoprecipitation, mobility shift, and reporter assays to investigate the relationship between Stat3 and PLK1. We used colony formation, fluorescence-activated cell sorting, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and xenograft tumor assays to determine the effects of increased activation of Stat3 and PLK1 in proliferation and survival of ESCC cells. RESULTS Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3. PLK1 then potentiated the expression of Stat3; β-catenin was involved in PLK1-dependent transcriptional activation of Stat3. This mutual regulation between Stat3 and PLK1 was required for proliferation of esophageal cancer cells and resistance to apoptosis in culture and as tumor xenografts in mice. Furthermore, phosphorylation of Stat3 and overexpression of PLK1 were correlated in a subset of ESCC. CONCLUSIONS Stat3 and PLK1 control each other's transcription in a positive feedback loop that contributes to the development of ESCC. Increased activity of Stat3 and overexpression of PLK1 promote survival and proliferation of ESCC cells in culture and in mice.

DOI: 10.1053/j.gastro.2011.11.023

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@article{Zhang2012ReciprocalAB, title={Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells.}, author={Yu Zhang and Xiao-li Du and Cheng-ji Wang and De-chen Lin and Xia Ruan and Yan-bin Feng and Yan-qiu Huo and Haiyong Peng and Jing-Lu Cui and Tong-tong Zhang and Yong-quan Wang and Hongbing Zhang and Qimin Zhan and Ming-rong Wang}, journal={Gastroenterology}, year={2012}, volume={142 3}, pages={521-530.e3} }