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谷胱甘肽S-转移酶M3和谷胱甘肽S-转移酶P1:驱动宫颈癌肿瘤进展的新因素

GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer.

作者信息

Checa-Rojas Alberto, Delgadillo-Silva Luis Fernando, Velasco-Herrera Martín Del Castillo, Andrade-Domínguez Andrés, Gil Jeovanis, Santillán Orlando, Lozano Luis, Toledo-Leyva Alfredo, Ramírez-Torres Alberto, Talamas-Rohana Patricia, Encarnación-Guevara Sergio

机构信息

Laboratorio de Proteómica, Centro de Ciencias Genómicas. Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

出版信息

Oncotarget. 2018 Apr 24;9(31):21696-21714. doi: 10.18632/oncotarget.24796.

Abstract

UNLABELLED

The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP. Furthermore, GSTM3 and GSTP1 knockdown showed that evasion of apoptosis was affected, and tumor proliferation was significantly reduced. Our data indicate the critical role of GST proteins in the regulation and progression of cervical cancer cells. Hence, we suggest GSTM3 and GSTP1 as novel biomarkers and potential therapeutic targets for treating cervical cancer.

SIGNIFICANCE

CC is particularly hazardous in the advanced stages, and there are few therapeutic strategies specifically targeting these stages. We performed analyses on CC tumor proteome dynamics and identified GSTM3 and GSTP1 as novel potential therapeutic targets. Knockdown of these proteins showed that they are involved in cell survival, cell proliferation and cellular evasion of apoptosis.

摘要

未标记

导致宫颈癌(CC)肿瘤进展(TP)的分子过程和蛋白质组学标志物要么未知,要么仅被部分理解。肿瘤进展会影响代谢和调节机制,这些机制可被识别为蛋白质组学变化。为了确定哪些蛋白质存在差异表达并了解癌症进展机制,我们分析了CC细胞系中肿瘤蛋白质组的动态变化。该分析揭示了在肿瘤进展过程中上调的两种蛋白质,即谷胱甘肽S-转移酶M3(GSTM3)和谷胱甘肽S-转移酶P1(GSTP1)。在肿瘤进展过程中,这些蛋白质通过核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAP激酶)途径参与细胞维持、细胞存活和细胞应激反应。此外,GSTM3和GSTP1基因敲低表明细胞凋亡逃避受到影响,肿瘤增殖显著降低。我们的数据表明谷胱甘肽S-转移酶蛋白在宫颈癌细胞的调控和进展中起关键作用。因此,我们建议将GSTM3和GSTP1作为治疗宫颈癌的新型生物标志物和潜在治疗靶点。

意义

宫颈癌在晚期特别危险,针对这些阶段的治疗策略很少。我们对宫颈癌肿瘤蛋白质组动态进行了分析,并确定GSTM3和GSTP1为新型潜在治疗靶点。这些蛋白质的基因敲低表明它们参与细胞存活、细胞增殖和细胞凋亡逃避。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d666/5955133/7a901af2701f/oncotarget-09-21696-g001.jpg

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