AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy
Changqing Wu, Chaoliu Dai, Xinyu Li, Mingju Sun, Hongwei Chu, Qiuhui Xuan, Yalei Yin, Chengnan Fang, Fan Yang, Zhonghao Jiang, Qing Lv, Keqing He, Yiying Qu, Baofeng Zhao, Ke Cai, Shuijun Zhang, Ranran Sun, Guowang Xu, Lihua Zhang, Siyu Sun, Yang Liu
Abstract
Our findings revealed that AKR1C3-dependent LD formation is critical for the adaptation to sorafenib in HCC through regulating lipid and energy homeostasis. AKR1C3-dependent LD accumulation protects HCC cells from sorafenib-induced mitochondrial lipotoxicity by regulating lipophagy. Targeting AKR1C3 might be a promising therapeutic strategy for HCC tumors.
Topics & Concepts
LipotoxicitySorafenibAutophagyLipid dropletCancer researchBiologyHepatocellular carcinomaLipid metabolismApoptosisCancer cellCell biologyChemistryBiochemistryCancerEndocrinologyInsulin resistanceInsulinGeneticsLipid metabolism and biosynthesisCancer, Hypoxia, and MetabolismMetabolomics and Mass Spectrometry Studies