title: Stat3 inhibits PTPN13 expression in squamous cell lung carcinoma through recruitment of HDAC5.
abstract: Proteins of the protein tyrosine phosphatase (PTP) family are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, and apoptosis. PTPN13 (also known as FAP1, PTPL1, PTPLE, PTPBAS, and PTP1E), a putative tumor suppressor, is frequently inactivated in lung carcinoma through the loss of either mRNA or protein expression. However, the molecular mechanisms underlying its dysregulation have not been fully explored. Interleukin-6 (IL-6) mediated Stat3 activation is viewed as crucial for multiple tumor growth and progression. Here, we demonstrate that PTPN13 is a direct transcriptional target of Stat3 in the squamous cell lung carcinoma. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HCC-1588 and SK-MES-1 cells inhibits PTPN13 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of PTPN13 and promotes its activity through recruiting HDAC5. Thus, our results suggest a previously unknown Stat3-PTPN13 molecular network controlling squamous cell lung carcinoma development.
authors.affiliation: The Helmholtz Sino-German Research Laboratory for Cancer, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Xiu-juan
authors.initials: XJ
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Xue
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Shao-jun
authors.initials: SJ
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Miao
authors.initials: M
authors.lastname: Lan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000096:biosynthesis* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; C404500:HDAC5 protein, human; D006655:Histone Deacetylases