CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxic

Abstract

Abstract Hypoxia is an essential feature of solid tumors. The regulatory network behind tumor cells in response to hypoxia environment is not completely comprehend. We ascertained the biochemical role of cell cycle division-related gene 8 (CDCA8) in bladder cancer (Bca) survival under hypoxia environment. In current study we revealed the expression of CDCA8 was considerably upraised in BCa. High expression level of CDCA8 was positive related with advanced Bca stage, advanced Bca stage grade and poor survival. Increased CDCA8 expression was decisive for Bca cells to survive in a hypoxic condition. CDCA8 enhanced the stabilization of HIF1α by competitively binding to AKT with PTEN and alleviating PTEN suppression to activate AKT phosphorylation, while HIF1α transcriptionally promote CDCA8 transcription, thus forming a positive feedback loop in Bca adaptation to oxygen-deficient environment. Collectively, CDCA8 promotes Bca survival under hypoxic environment by activating AKT/GSK3β signaling pathway and heightening the stabilization of HIF1α. CDCA8 is critical for Bca to adapt to oxygen deprivation and may provide a novel thinking for Bca treatment.