MSX1 inhibits cell migration and invasion through regulating the Wnt/β-catenin pathway in glioblastoma.

Abstract

Glioblastoma is a type of primary brain tumor with poor prognosis. The hallmark phenotype of glioblastoma is its aggressive invasion. Understanding the molecular mechanism of the invasion behavior of glioblastoma is essential for the development of effective treatment of the disease. In our present study, we found that the expression levels of a homeobox transcription factor, MSX1, were significantly reduced in glioblastoma compared to normal brain tissues. The levels of MSX1 in glioblastoma tissues were also correlated with the survival of the patients. In cultured glioblastoma cells, MSX1 was a negative regulator of cell migration and invasion. Loss of MSX1 enhanced cell migration and induced mesenchymal transition as characterized by the downregulation of E-cadherin and the upregulation of N-cadherin. Overexpression of MSX1 on the other hand led to the inhibition of both cell migration and mesenchymal transition. We also found that MSX1 was able to inhibit the Wnt/β-catenin signaling pathway, and that the ability to regulate the Wnt/β-catenin signaling pathway is critical for MSX1 to suppress glioblastoma cell migration and invasion.