1. Reciprocal Activation Between PLK1 and Stat3 Contributes to Survival and Proliferation of Esophageal Cancer Cells
- Author
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Yu Zhang, Yan Bin Feng, Ming Rong Wang, Yan–Qiu Huo, Hongbing Zhang, Cheng–Ji Wang, Xiaoli Du, Qi min Zhan, Xia Ruan, Haiyong Peng, Yong–Quan Wang, De-Chen Lin, Tong–Tong Zhang, and Jing–Lu Cui
- Subjects
Time Factors ,Esophageal Neoplasms ,Cell ,Cell Cycle Proteins ,Electrophoretic Mobility Shift Assay ,Cell Separation ,medicine.disease_cause ,Mice ,Genes, Reporter ,Phosphorylation ,STAT3 ,beta Catenin ,Feedback, Physiological ,Reverse Transcriptase Polymerase Chain Reaction ,Pteridines ,Gastroenterology ,Transfection ,Flow Cytometry ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Carcinoma, Squamous Cell ,Female ,RNA Interference ,Signal Transduction ,STAT3 Transcription Factor ,Transcriptional Activation ,Chromatin Immunoprecipitation ,Cell Survival ,Blotting, Western ,Mice, Nude ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,Biology ,Real-Time Polymerase Chain Reaction ,PLK1 ,Gene Expression Regulation, Enzymologic ,Cell Line, Tumor ,Proto-Oncogene Proteins ,In Situ Nick-End Labeling ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,Cell Proliferation ,Hepatology ,Xenograft Model Antitumor Assays ,Enzyme Activation ,Cell culture ,NIH 3T3 Cells ,biology.protein ,STAT protein ,Cancer research ,Carcinogenesis ,Chromatin immunoprecipitation - 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.
- Published
- 2012