The Epithelial-to-Mesenchymal Transition-Like Process in Glioblastoma: An Updated Systematic Review and In Silico Investigation.
Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer due to its highly invasive nature that impedes the surgical removal of all tumor cells, making relapse inevitable. However, the mechanisms used by glioma cells to invade the surrounding tissue are still unclear. In this context, epithelial-to-mesenchymal transition (EMT) has emerged as a key regulator of this invasive state and although the real relevance of this program in malignant glioma is still controversial, it has been strongly associated with GBM malignancy. EMT is a very complex process regulated by several families of transcriptional factors through many signaling pathways that form a network that allows cancer cells to acquire invasive properties and penetrate the neighboring stroma, resulting in the formation of an advantageous microenvironment for cancer progression and metastasis. In this systematic review, we focus on the molecular mechanisms of EMT including EMT-factors, drug resistance, miRNA, and new therapeutic strategies. In addition, we address controversial questions about mesenchymal shift in GBMs with a bioinformatics analysis to show that in terms of epithelial and mesenchymal phenotype, the majority of GBMs samples analyzed have a profile more mesenchymal than epithelial. If induced, this phenotype can be shifted toward an even more mesenchymal phenotype in an EMT-like process in glioma cells. A better understanding of the molecular regulation of the EMT during tumor spreading will help to provide potential therapeutic interventions to target this program when treating GBM.
Departamento de Ciências Básicas da Saúde e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil.
Isabele C
IC
Iser
Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Mariana B
MB
Pereira
Departamento de Biofísica e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Guido
G
Lenz
Departamento de Ciências Básicas da Saúde e Laboratório de Biologia Celular, Universidade Federal de Ciências da Saúde de Porto Alegre - UFCSPA, Porto Alegre, RS, Brazil.
Márcia R
MR
Wink
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D003198:Computer Simulation; D058750:Epithelial-Mesenchymal Transition; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans
EMT-like; epithelial-to-mesenchymal transition; glioblastoma multiforme; transcriptome analysis