Palmitic acid activates GPRs/KLF7/HEY1 signal axis to promote the occurrence and development of endometrial carcinoma
Obesity is a high-risk factor in the development of endometrial carcinoma (EC), but the specific molecular mechanisms of EC induced by obesity are unclear. The increase of palmitic acid (PA) in serum after obesity is closely associated with the progression of many kinds of tumors. Our previous study observed that high concentration of PA could significantly enhance the proliferation, invasion and migration of EC cells. It has been shown that GPR40/120 is a specific receptor of PA. In this study, based on the culture of EC cells Ishikawa in vitro, we found that PA could promote the proliferation, invasion and migration ability of cancer cells by activating GPR40/120 to up-regulate KLF7 expression. The experiment of RNA-Seq combined with double luciferase reporter gene confirmed that HEY1 may be the key downstream target gene for KLF7 to promote the progression of EC. Finally, on the basis of constructing the model of obese mice with EC tumor, and collecting the endometrial tissues of EC patients and non-cancer individuals, we verified in vivo that increased PA content after obesity promotes the development of EC by activating the GPRs/KLF7/HEY1 signaling axis. This study provides a theoretical basis for elucidating the molecular mechanism of the occurrence and development of endometrial cancer caused by obesity, and also provides basic data for screening new drug targets for the treatment of endometrial cancer.