The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor.
Prognostic implications of epithelial to mesenchymal transition related proteins (E-cadherin, Snail) and hypoxia inducible factor 1α in endometrioid endometrial carcinoma.
Using ovarian and endometrial cancer cell lines, we observed that TM downregulates HIF-1α protein levels and HIF-transcriptional targets involved in tumor angiogenesis and glycolysis, but did not affect HIF-1α protein synthesis.
HIF-1 (hypoxia-inducible factor 1) activation is critical for the metabolic reprogramming and progression of solid tumors, and DEC2 (differentiated embryonic chondrocyte gene 2) has been recently reported to suppress HIF-1 in human breast and endometrial cancers.
Here we show that upregulation of SHARP1 suppressed tumor angiogenesis by decreasing hypoxia-inducible factor-1α (HIF-1α), inhibited cell viability and tumor growth in EC.
To test the hypothesis that restoring HIF-1alpha in cultured cells would restore the ability of E(2) to induce VEGF expression, we treated human endometrial cancer cells (ECC-1) with cobalt chloride (CoCl(2);100 microm), which prevents oxygen-induced HIF-1alpha degradation.
The angiogenic mediator HIF-1alpha, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers.