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.

卵巢癌以高复发率为特征，亟需开发新型治疗策略以改善患者预后。其中一项潜在策略便是诱导卵巢癌细胞发生铁死亡（ferroptosis）。铁死亡是一种铁依赖性、由脂质过氧化驱动的细胞死亡模式，主要发生于细胞膜之上。PTRF是定位于细胞膜的细胞质膜微囊（caveolae）结构的固有组成成分，参与诸多生理过程，包括但不限于内吞作用、信号转导以及脂质代谢。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。本研究通过小干扰RNA（siRNA）在卵巢癌细胞系HEY与SKOV3中敲低PTRF的表达，随后使用埃拉斯汀（Erastin，Era）诱导铁死亡。研究结果表明，PTRF缺失可增强癌细胞对铁死亡的敏感性，其潜在机制可能是通过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，包括脂质与动脉粥样硬化、流体切应力以及动脉粥样硬化相关通路。本研究发现为卵巢癌新型治疗手段的开发提供了新的思路。