GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer
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Alberto Checa-Rojas1, Luis Fernando Delgadillo-Silva1, Martín del Castillo Velasco-Herrera1, Andrés Andrade-Domínguez1, Jeovanis Gil1, Orlando Santillán2, Luis Lozano2, Alfredo Toledo-Leyva3, Alberto Ramírez-Torres1, Patricia Talamas-Rohana3 and Sergio Encarnación-Guevara1
1Laboratorio de Proteómica, Centro de Ciencias Genómicas. Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
2Programa de Genómica Evolutiva, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
3Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, México
Sergio Encarnación-Guevara, email: [email protected]
Keywords: GSTP1; GSTM3; cervical cancer; morpholinos; targets genes
Received: August 13, 2017 Accepted: March 01, 2018 Published: April 24, 2018
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.
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