title: STAT3alpha is oncogenic for endometrial carcinoma cells and mediates the oncogenic effects of autocrine human growth hormone.
abstract: We herein demonstrate an oncogenic role for signal transducer and activator of transcription (STAT)-3alpha (the full length STAT3 isoform), which also mediates autocrine human GH (hGH)-stimulated oncogenicity, in human endometrial carcinoma (EC) cells. Autocrine hGH stimulated Y705 phosphorylation of STAT3 and STAT3-mediated transcriptional activity in a SRC and Janus-2 Kinase dependent manner in human EC cell lines. Forced expression of a constitutively active variant of STAT3alpha increased proliferation, anchorage-independent, three-dimensional (3D) Matrigel, and xenograft growth and promoted epithelial-mesenchymal transition, migration, and invasion of EC cells. Conversely, the oncogenic capacity of EC cells was significantly impaired by treatment with JSI-124, an inhibitor of STAT3 phosphorylation and activity, small interfering RNA-mediated depletion of STAT3alpha, or a dominant-negative variant of STAT3alpha. Furthermore, the enhanced EC cell oncogenicity stimulated by autocrine hGH, was also abrogated by functional inhibition or small interfering RNA-mediated depletion of STAT3alpha. STAT3alpha may therefore be a common mediator of oncogenic signaling pathways stimulating progression of EC.
authors.affiliation: Liggins Institute, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Tang
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Kong
authors.forename: Arindam
authors.initials: A
authors.lastname: Banerjee
authors.forename: Nethaji
authors.initials: N
authors.lastname: Muniraj
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.forename: Michael
authors.initials: M
authors.lastname: Steiner
authors.forename: Jo K
authors.initials: JK
authors.lastname: Perry
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Liu
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; D014315:Triterpenes; C405010:delta-hGHR; D019382:Human Growth Hormone; C038106:cucurbitacin I