1. Academic Validation
  2. TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions

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

  • Sci Rep. 2020 Aug 25;10(1):14151. doi: 10.1038/s41598-020-70822-4.
Wei Yang  # 1 Peng-Fei Wu  # 2 Jian-Xing Ma 2 Mao-Jun Liao 2 Lun-Shan Xu 3 Liang Yi 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, P.R. China.
  • 2 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, 10# Changjiangzhi Road, Daping, Yuzhong District, Chongqing, 400042, China.
  • 3 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, 10# Changjiangzhi Road, Daping, Yuzhong District, Chongqing, 400042, China. xuliu559@163.com.
  • 4 Department of Neurosurgery, Daping Hospital and Institute Research of Surgery, Army Medical University, 10# Changjiangzhi Road, Daping, Yuzhong District, Chongqing, 400042, China. yiliangcq@126.com.
  • # Contributed equally.
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.

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  • HY-12755
    99.87%, Cdc42 GTPase 抑制剂