title: Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells.
abstract: OBJECTIVE
  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.
authors: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors: Yu
authors: Y
authors: Zhang
authors: Xiao-Li
authors: XL
authors: Du
authors: Cheng-Ji
authors: CJ
authors: Wang
authors: De-Chen
authors: DC
authors: Lin
authors: Xia
authors: X
authors: Ruan
authors: Yan-Bin
authors: YB
authors: Feng
authors: Yan-Qiu
authors: YQ
authors: Huo
authors: Haiyong
authors: H
authors: Peng
authors: Jing-Lu
authors: JL
authors: Cui
authors: Tong-Tong
authors: TT
authors: Zhang
authors: Yong-Quan
authors: YQ
authors: Wang
authors: Hongbing
authors: H
authors: Zhang
authors: Qi-Min
authors: QM
authors: Zhan
authors: Ming-Rong
authors: MR
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D025461:Feedback, Physiological; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011621:Pteridines / Q000494:pharmacology; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D015533:Transcriptional Activation; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D050796:STAT3 Transcription Factor; D051176:beta Catenin; D000097869:Polo-Like Kinase 1; C518477:BI 2536; C495270:CTNNB1 protein, human; C494086:STAT3 protein, human