TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
Autor: | Mao-jun Liao, Jian-xing Ma, Lunshan Xu, Pengfei Wu, Wei Yang, Liang Yi |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Molecular biology Wiskott-Aldrich Syndrome Protein Neuronal CDC42 Kaplan-Meier Estimate Metastasis Mice 0302 clinical medicine Pseudopodia cdc42 GTP-Binding Protein Cancer Multidisciplinary biology Chemistry Brain Neoplasms Drug discovery Wiskott–Aldrich syndrome protein Prognosis Neoplasm Proteins Invadopodia Heterografts Medicine Female Signal Transduction Cell biology Science Motility Mice Nude TRPV Cation Channels Article 03 medical and health sciences Downregulation and upregulation Glioma Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness neoplasms medicine.disease Actins Rats nervous system diseases 030104 developmental biology HEK293 Cells Cancer cell biology.protein Cancer research Glioblastoma 030217 neurology & neurosurgery |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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