Format

Send to

Choose Destination
Front Biosci (Landmark Ed). 2019 Mar 1;24:1060-1070.

BMP4 inhibits glioblastoma invasion by promoting E-cadherin and claudin expression.

Author information

1
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
2
Department of Neurosurgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolian Autonomous Region, China.
3
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China, chenqx666@whu.edu.cn.

Abstract

Glioblastoma multiforme (GBM) is a brain tumor that deeply infiltrates adjacent tissues and causes significant mortality. Thus, understanding the mechanisms that derive the invasion of brain tissue by GBM might help the treatment of this cancer. To this end, we examined the impact of BMP4 on invasion of GBM. In this study, Human GBM samples, GBM cells and human orthotopic GBM-xenografted animal model, quantitative PCR, immunostaining, immunoblotting, Scratch wound and transwell assays were used to detect the effect and the mechanism of BMP4 in GBM cells. BMP4 expression was found to positively correlate with E-cadherin and claudin expression in human GBM samples. Elevation or suppression of BMP4 expression resulted in a respective increase or decrease in E-cadherin and claudin levels, both in vitro and in vivo. Suppression of BMP4 expression was associated with enhanced GBM cell migration and invasion, while BMP4 overexpression inhibited these processes. Smad1/5/8 protein phosphorylation positively correlated with BMP4 expression. Pharmacological blockade of Smad1/5/8 phosphorylation impaired BMP4-dependent inhibition of cell migration and invasion. Together, these findings suggest that BMP4 increases E-cadherin and claudin expression in GBM through activation of SMAD signaling, thereby suppressing tumor cell invasion.

PMID:
30844730

Supplemental Content

Full text links

Icon for Frontiers in Bioscience
Loading ...
Support Center