Abstract
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.SignificanceCC 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.
Highlights
Cervical cancer (CC) is still the second most common cancer-related death in women worldwide, it is in theory a preventable disease [1]
We developed a UV stress sensitivity assay in an MDA-MB-231 cell line that was negative for HPV18, GSTM3 and GSTP1 [22] (Supplementary Figure 4A), using recombinant glutathione S-transferase (GST) and HPV18 E7 to perform at phenotype analysis through exogenous protein complementation (PAEP)
We observed that two members of the GST (GSTM3 and GSTP1) family had increased expression throughout the time period
Summary
Cervical cancer (CC) is still the second most common cancer-related death in women worldwide, it is in theory a preventable disease [1]. The most common treatment includes a concurrent cisplatinbased chemoradiation therapy. This treatment is regularly the only option for treating advanced stage www.oncotarget.com cancers, in most cases it fails to fully eradicate the disease [4, 5]. Target gene-based strategies in cervical cancer remain promising; the research efforts of these therapies are aimed at prevention or early stages [9, 10]. In this sense, specific target gene-based strategies for late-stages or tumor progression are still urgently needed in the clinical setting [11]
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