Regulation of cancer cell ferroptosis by PTRF/Cavin-1

Ovarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cells to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress, and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.

卵巢癌复发率较高，亟需新型治疗策略以改善患者预后。诱导卵巢癌细胞发生铁死亡（ferroptosis）便是潜在治疗策略之一。铁死亡是一种铁依赖性、脂质过氧化驱动的细胞死亡模式，主要发生于细胞膜。PTRF作为定位于细胞膜的细胞质膜微囊（caveolae）结构的整合组分，参与包括胞吞作用、信号转导及脂质代谢在内的多种生理过程。本研究阐明了卵巢癌中PTRF与铁死亡之间的关联，为新型治疗策略的开发提供了全新视角。本研究采用小干扰RNA（siRNA）敲低卵巢癌细胞系HEY与SKOV3中的PTRF表达，随后使用艾拉司他（Erastin，简称Era）诱导细胞发生铁死亡。研究结果表明，PTRF缺失可使癌细胞对铁死亡更为敏感，其潜在机制可能为改变细胞膜稳定性与膜张力，进而影响与铁死亡相关的信号通路，如脂质与动脉粥样硬化、流体剪切应力及动脉粥样硬化通路。本研究发现为卵巢癌新型治疗手段的开发提供了新的理论依据。