HIF-2 alpha-induced upregulation of CD36 promotes the development of ccRCC

Clear cell renal cell carcinoma (ccRCC) is characterized by the abundance of lipid droplets and the activation of the hypoxia-inducible factor (HIF) signaling pathway. However, the lipid reprogramming induced by HIF signaling in ccRCC is not fully understood. In this study, we found that the fatty acid receptor CD36 was highly expressed in human ccRCC tissues and ccRCC cell lines. CD36 overexpression increased fatty acid uptake and lipid droplet formation, and enhanced the proliferation and migration of ccRCC cells in a DGAT1-dependent manner. In contrast, the disruption of endogenous CD36 showed the opposite effects. The upregulated expres-sion of CD36 in ccRCC was associated with hypoxia and HIF-2 alpha activation. Furthermore, we identified CD36 as a new target of the transcription factor HIF-2 alpha. The knockdown of CD36 in ccRCC cells reduced lipid accumulation and also blocked the tumor-promoting effects induced by HIF-2 alpha under hypoxia. Our findings suggest that hypoxia-dependent HIF-2 alpha promotes the remodeling of lipid metabolism and the malignant phenotype of ccRCC via CD36, providing a certain theoretical basis for clarifying the mechanism of ccRCC.

Automated summary

This study found that the fatty acid receptor CD36 is highly expressed in ccRCC tissues and cell lines, and its overexpression enhances fatty acid uptake, lipid droplet formation, proliferation, and migration of ccRCC cells. CD36 upregulation in ccRCC is associated with hypoxia and HIF-2 alpha activation. Knockdown of CD36 in ccRCC cells reduces lipid accumulation and blocks the tumor-promoting effects of HIF-2 alpha under hypoxia.