ATGL promotes the proliferation of cervical cancer cells by pseudo-hypoxia mediated Warburg effect

Highly proliferative cancer cells adapt to the increased energy demand by reprogramming their metabolism towards aerobic glycolysis, a phenomenon known as the "Warburg effect". However, in the last decade, the concept of metabolic rewiring as a cancer hallmark has been expanded including lipid metabolism as well. In the cancer scenario, lipids form membranes building blocks, signaling molecules, and post-translational modification of proteins. Several pieces of evidence have also emerged about the role of lipases in cancer. HSL and MAGL dysregulations have been associated with cancer and related comorbidities; in contrast, the role of the triacylglycerol rate-limiting lipase ATGL is less clear. Here, bioinformatic analyses evidenced higher expression of ATGL in human cervical cancer as well as the positive correlation between ATGL expression and aggressiveness of the tumor. Interestingly, ATGL-mediated activation of HIF1α has been disclosed in the cervical cancer cell lines HeLa and Me-180. In particular, ATGL increased ROS levels activating HIF1α, which is responsible for higher proliferation and glycolytic rate. Overall, data reported in this work reveal a new pro-tumor feature for ATGL in cervical cancer, which could be affected by the cellular ability to scavenge ROS. This evidence could be exploited to clarify the controversial role of ATGL in cancer and to develop new personalized therapeutic strategies.