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YAP controls cell migration and invasion through a Rho GTPase switch.

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|May 27, 2025
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The transcriptional coactivator YAP promotes cell migration by activating TRIO, leading to Rac1 activation and RhoA inhibition. This YAP-TRIO-Rho signaling pathway is crucial for cell invasion, particularly in glioblastoma.

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Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Cell movement is fundamental to physiological and pathological processes.
  • The transcriptional coactivator YAP plays roles in development and is linked to cancer metastasis.
  • Rho family GTPases (Rac1, RhoA) are critical regulators of cytoskeletal dynamics and cell motility.

Purpose of the Study:

  • To elucidate the mechanisms by which YAP controls cell migration.
  • To investigate the role of YAP in modulating Rho GTPase signaling.
  • To explore the therapeutic potential of targeting the YAP pathway in cancer, especially glioblastoma.

Main Methods:

  • Investigated YAP's transcriptional regulation of TRIO via intronic enhancer binding.
  • Assessed the impact of YAP-TRIO signaling on Rac1 and RhoA activation.
  • Evaluated cell migration and invasion in vitro and in vivo.
  • Analyzed gene expression signatures (YAP, TRIO, STAT3) in patient glioblastoma samples.

Main Results:

  • YAP directly transactivated TRIO, a Rac1 guanine nucleotide exchange factor.
  • YAP-induced TRIO activation led to Rac1 activation and RhoA inhibition, enhancing cell migration and invasion.
  • This YAP-dependent pathway was observed in various cell types and was particularly pronounced in glioblastoma.
  • YAP-TRIO signaling activated STAT3, suggesting pathway cross-talk that may promote invasive growth.

Conclusions:

  • The YAP-TRIO-Rho-GTPase signaling network is a key regulator of invasive cell spread.
  • Hyperactivation of YAP, TRIO, and STAT3 is associated with poor patient survival in glioblastoma.
  • Targeting this pathway may offer therapeutic strategies for invasive cancers.