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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.

DOI:10.1080/10715762.2024.2386457
PMID:39079051
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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Regulation of cancer cell ferroptosis by PTRF/Cavin-1.PTRF/Cavin-1 调控癌细胞铁死亡。
Free Radic Res. 2024 May-Jun;58(6-7):417-429. doi: 10.1080/10715762.2024.2386457. Epub 2024 Aug 7.
2
PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function.PTRF-Cavin,一种小窝形成和功能所需的保守细胞质蛋白。
Cell. 2008 Jan 11;132(1):113-24. doi: 10.1016/j.cell.2007.11.042.
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Iron Administration Overcomes Resistance to Erastin-Mediated Ferroptosis in Ovarian Cancer Cells.铁剂给药克服卵巢癌细胞对埃拉司亭介导的铁死亡的抗性。
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IGF-IR internalizes with Caveolin-1 and PTRF/Cavin in HaCat cells.IGF-IR 与 Caveolin-1 和 PTRF/Cavin 在 HaCat 细胞中内化。
PLoS One. 2010 Nov 30;5(11):e14157. doi: 10.1371/journal.pone.0014157.
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Polymerase I and transcript release factor (PTRF)/cavin-1 is a novel regulator of stress-induced premature senescence.聚合酶 I 和转录释放因子(PTRF)/钙卫蛋白-1 是一种新的应激诱导过早衰老的调节因子。
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SNAI2 promotes the development of ovarian cancer through regulating ferroptosis.SNAI2 通过调控铁死亡促进卵巢癌的发展。
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PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9.PTRF-cavin-1 表达降低 PC3 前列腺癌细胞的迁移:基质金属蛋白酶 9 的作用。
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Squalene monooxygenase (SQLE) protects ovarian cancer cells from ferroptosis.鲨烯单加氧酶(SQLE)可保护卵巢癌细胞免受铁死亡。
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Down-regulation of the cavin family proteins in breast cancer.乳腺癌中腔蛋白家族的下调。
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Activation of the reverse transsulfuration pathway through NRF2/CBS confers erastin-induced ferroptosis resistance.通过 NRF2/CBS 激活反硫途径赋予依维莫司诱导的铁死亡抗性。
Br J Cancer. 2020 Jan;122(2):279-292. doi: 10.1038/s41416-019-0660-x. Epub 2019 Dec 10.

引用本文的文献

1
Targeting ferroptosis: a promising avenue for ovarian cancer treatment.靶向铁死亡:卵巢癌治疗的一条有前景的途径。
Front Immunol. 2025 Jun 5;16:1578723. doi: 10.3389/fimmu.2025.1578723. eCollection 2025.