Cobalt chloride-mediated protein kinase Cα (PKCα) phosphorylation induces hypoxia-inducible factor 1α (HIF1α) in the nucleus of gastric cancer cell

Abstract Hypoxia promotes cancer progression, and metastasis. The major protein expressed in hypoxic solid cancer is hypoxia-inducible factor 1 (HIF1). We show that enhanced phosphorylation of a conventional protein kinase C isoform, PKCα, at threonine 638 (T 638 ) by hypoxia-mimetic cobalt chloride induces HIF1α in nuclei of gastric epithelial cells (GECs). Moreover, phospho-T 638 -PKCα (P-PKCα) interacts with p300-HIF1α complex in the nuclei of hypoxic GECs and PKCα phosphorylation at T 638 enhances transcriptional activity of HIF1α. High P-PKCα expression in neoplastic gastric cancer biopsy samples as compared to nonneoplastic samples suggests that P-PKCα might act as an indicator of gastric cancer progression.