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PTRF/Cavin-1 调控癌细胞铁死亡。

Regulation of cancer cell ferroptosis by PTRF/Cavin-1.

机构信息

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.

出版信息

Free Radic Res. 2024 May-Jun;58(6-7):417-429. doi: 10.1080/10715762.2024.2386457. Epub 2024 Aug 7.

Abstract

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.

摘要

卵巢癌复发率高,需要新的治疗策略来改善患者的预后。一种潜在的策略是诱导卵巢癌细胞发生铁死亡。铁死亡是一种铁依赖性、脂质过氧化驱动的细胞死亡方式,主要发生在细胞膜上。PTRF 是位于细胞膜上的 caveolae 结构的一个组成部分,参与多种生理过程,包括但不限于内吞作用、信号转导和脂质代谢。本研究阐明了 PTRF 与卵巢癌细胞铁死亡之间的关系,为开发新的治疗策略提供了新的视角。我们使用 siRNA 在卵巢癌细胞系 HEY 和 SKOV3 中敲低 PTRF,然后用 Erastin (Era) 刺激铁死亡。我们的研究表明,PTRF 的缺失使癌细胞对铁死亡敏感,可能通过改变膜的稳定性和张力,从而影响与铁死亡相关的信号通路,如脂质和动脉粥样硬化、流体切应力和动脉粥样硬化。我们的发现为开发治疗卵巢癌的新方法提供了新的思路。

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