Int J Biol Sci 2019; 15(2):395-403. doi:10.7150/ijbs.27256
SENP1 Interacts with HIF1α to Regulate Glycolysis of Prostatic Carcinoma Cells
1. Department of Urology, the First Affiliated Hospital of Harbin Medical University, Harbin, China
2. Department of Breast Surgery, the Third Affiliated Hospital of Harbin Medical, University, Harbin, China
Wang C, Tao W, Ni S, Chen Q. SENP1 Interacts with HIF1α to Regulate Glycolysis of Prostatic Carcinoma Cells. Int J Biol Sci 2019; 15(2):395-403. doi:10.7150/ijbs.27256. Available from http://www.ijbs.com/v15p0395.htm
Background: Hypoxic microenvironment inside the tumor forces tumor cells to up-regulate the glycolytic pathway to maintain a sufficient energy supply for tumor growth. Activation of HIF1α under hypoxia condition is able to regulate the expression of glycolysis-related genes, and results in the proliferation and metastasis of cancer cells. However, the mechanism underlying HIF1α activation and glycolysis induction by hypoxia remains unclear. The present study is aimed to test if SENP1 regulates the glycolysis of prostate cancer cells (CaP) by improving stability of HIF1α protein.
Methods: We employed qPCR and western blotting assay to analyze expression of HIF1α and SENP1. Glucose uptake assay, lactate production assay, LDH release assay and ATP production assay were utilized to evaluate cell glycolysis. The interaction between SENP1 and HIF1α was verified by co-immunoprecipitation assay.
Results: We found that hypoxia condition improves glucose uptake and lactate production to sustain sufficient ATP for cellular activity in prostatic carcinoma cells. The expression of SENP1 mRNA was significantly increased in human prostatic carcinoma cell lines after exposure to hypoxia, accompanied by the up-regulation of HIF1α. Furthermore, forced expression of SENP1 was shown to regulate the glycolysis in prostatic carcinoma cells by stabilizing HIF1α. The up-regulation of SENP1 promotes tumor cell proliferation and tumorgenesis by interacting with HIF1α which was deSUMOylated and sequentially leading to a “Warburg effect”.
Conclusion: SENP1 interacts with HIF1α to regulate glycolysis and proliferation of prostatic carcinoma cells under hypoxia condition, which provides new insights into prostatic carcinoma therapy.
Keywords: SENP1, HIF1α, glycolysis, prostatic carcinoma, tumorgenesis.