Related Experiment Video

Updated: Mar 15, 2026

Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts

Published on: August 27, 2012

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The Extracellular Matrix Regulates Invasion in Fusion-Negative Rhabdomyosarcoma via YAP-PIEZO1 Signaling Axis

Yuanzhong Pan1, Juha Kim1, Brian M Wong1

  • 1Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Cancers
|March 14, 2026
PubMed

Insights

Extracellular matrix density drives fusion-negative rhabdomyosarcoma (FNRMS) invasion via the YAP-PIEZO1 pathway. Targeting this mechanosensitive axis offers a potential therapeutic strategy for aggressive FNRMS.

Area of Science:

  • Oncology
  • Cell Biology
  • Biophysics

Background:

  • Fusion-negative rhabdomyosarcoma (FNRMS) is the most common pediatric soft-tissue sarcoma.
  • Tumor invasion in FNRMS correlates with poor prognosis and recurrence, but mechanisms are poorly understood.
  • Investigating the role of extracellular matrix density in FNRMS progression via mechano-transduction.

Purpose of the Study:

  • To elucidate the mechanism by which extracellular matrix density influences FNRMS cell invasion.
  • To identify key molecular players in the mechano-transduction pathway regulating FNRMS progression.
  • To explore the therapeutic potential of targeting identified pathways in FNRMS.

Main Methods:

  • Utilized three-dimensional spheroid invasion assays with FNRMS cells in varying collagen densities.
  • Employed immunofluorescence, gene sequencing, live-cell calcium imaging, and pharmacological inhibition.
  • Focused on the YAP-PIEZO1 signaling axis.

Main Results:

  • High extracellular matrix density significantly increased FNRMS invasive spreading and YAP nuclear localization.
  • YAP activation promoted invasion, while inhibition attenuated matrix-enhanced invasion.
  • Identified PIEZO1 as a direct YAP target; PIEZO1-dependent calcium influx was crucial for invasion.
  • Elevated PIEZO1 expression correlated with poorer patient survival.
  • Targeting YAP inhibited calcium flux and FNRMS invasion.

Conclusions:

  • Established a YAP-PIEZO1 signaling axis linking extracellular matrix density to FNRMS invasion.
  • This mechanosensitive pathway represents a potential therapeutic vulnerability in aggressive FNRMS.
  • Findings suggest novel therapeutic strategies targeting mechano-transduction in FNRMS.
Keywords:
PIEZO1YAPcalcium signalingextracellular matrixfusion-negative rhabdomyosarcomainvasionspheroid

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