TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

Abstract The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metasta...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wei Yang, Peng-fei Wu, Jian-xing Ma, Mao-jun Liao, Lun-shan Xu, Liang Yi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0504ec51c83a47389dc2d5bd205e65c0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0504ec51c83a47389dc2d5bd205e65c0
record_format	dspace
spelling	oai:doaj.org-article:0504ec51c83a47389dc2d5bd205e65c02021-12-02T19:02:32ZTRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions10.1038/s41598-020-70822-42045-2322https://doaj.org/article/0504ec51c83a47389dc2d5bd205e65c02020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70822-4https://doaj.org/toc/2045-2322Abstract The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.Wei YangPeng-fei WuJian-xing MaMao-jun LiaoLun-shan XuLiang YiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei Yang Peng-fei Wu Jian-xing Ma Mao-jun Liao Lun-shan Xu Liang Yi TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
description	Abstract The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.
format	article
author	Wei Yang Peng-fei Wu Jian-xing Ma Mao-jun Liao Lun-shan Xu Liang Yi
author_facet	Wei Yang Peng-fei Wu Jian-xing Ma Mao-jun Liao Lun-shan Xu Liang Yi
author_sort	Wei Yang
title	TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
title_short	TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
title_full	TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
title_fullStr	TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
title_full_unstemmed	TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
title_sort	trpv4 activates the cdc42/n-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0504ec51c83a47389dc2d5bd205e65c0
work_keys_str_mv	AT weiyang trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions AT pengfeiwu trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions AT jianxingma trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions AT maojunliao trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions AT lunshanxu trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions AT liangyi trpv4activatesthecdc42nwasppathwaytopromoteglioblastomainvasionbyalteringcellularprotrusions
_version_	1718377247449022464

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

Ejemplares similares