IMR Press / FBL / Volume 24 / Issue 6 / DOI: 10.2741/4768

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
BMP4 inhibits glioblastoma invasion by promoting E-cadherin and claudin expression
Show Less
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 Central laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
*Correspondence: chenqx666@whu.edu.cn (Qianxue Chen)
Front. Biosci. (Landmark Ed) 2019, 24(6), 1060–1070; https://doi.org/10.2741/4768
Published: 1 March 2019
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
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.

Keywords
Glioblastoma Multiforme
Invasion
BMP4
pSmad1/5/8
E-cadherin
Claudin
Figures
Figure 1.
Share
Back to top