GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer.
GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer.
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DOI：
10.18632/oncotarget.24796
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发表时间：
2018-04-24
期刊：
影响因子：
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通讯作者：
Encarnación-Guevara S
中科院分区：
文献类型：
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作者：
Checa-Rojas A;Delgadillo-Silva LF;Velasco-Herrera MDC;Andrade-Domínguez A;Gil J;Santillán O;Lozano L;Toledo-Leyva A;Ramírez-Torres A;Talamas-Rohana P;Encarnación-Guevara S
导致宫颈癌 (CC) 肿瘤进展 (TP) 的分子过程和蛋白质组标记要么未知，要么仅部分了解。 TP 影响代谢和调节机制，这些机制可被识别为蛋白质组变化。为了确定哪些蛋白质差异表达并了解癌症进展的机制，我们分析了 CC 细胞系中肿瘤蛋白质组的动态。该分析揭示了 TP 期间上调的两种蛋白质：GSTM3 和 GSTP1。这些蛋白质在 TP 期间通过 NF-κB 和 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敲低表明细胞凋亡的逃避受到影响，肿瘤增殖显着减少。我们的数据表明 GST 蛋白在宫颈癌细胞的调节和进展中发挥着关键作用。因此，我们建议 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。 CC 在晚期阶段尤其危险，并且很少有专门针对这些阶段的治疗策略。我们对 CC 肿瘤蛋白质组动力学进行了分析，并将 GSTM3 和 GSTP1 确定为新的潜在治疗靶点。这些蛋白质的敲低表明它们参与细胞存活、细胞增殖和细胞凋亡的逃避。
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. 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.