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.

卵巢癌复发率居高不下，亟需开发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、脂质过氧化驱动的细胞死亡方式，主要发生于细胞膜上。PTRF作为细胞膜上穴样凹陷（caveolae）结构的核心组成成分，参与诸多生理过程，涵盖但不限于内吞作用、信号转导及脂质代谢。本研究阐明了卵巢癌中PTRF与铁死亡的关联，为新型治疗策略的研发提供了全新视角。本研究通过小干扰RNA（siRNA）敲低卵巢癌细胞系HEY与SKOV3中的PTRF表达，随后使用艾拉司他丁（Erastin，Era）诱导铁死亡。研究结果显示，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，包括脂质代谢、动脉粥样硬化、流体切应力及动脉粥样硬化。本研究结果为卵巢癌新型治疗方案的开发提供了新的研究思路与理论支撑。