STAT3α Is Oncogenic for Endometrial Carcinoma Cells and Mediates the Oncogenic Effects of Autocrine Human Growth Hormone

We herein demonstrate an oncogenic role for signal transducer and activator of transcription (STAT)-3α (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 STAT3α 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 STAT3α, or a dominant-negative variant of STAT3α. Furthermore, the enhanced EC cell oncogenicity stimulated by autocrine hGH, was also abrogated by function...