The YAP1 and EPHA3 receptor tyrosine kinase axis regulates cellular plasticity and treatment response

Marwah M Al-Mathkour1, Abdulrahman M Dwead2, Kezhan Kazaw3

  • 1Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, United States of America; Miller School of Medicine, University of Miami, Miami, FL, United States of America.

Cellular Signalling
|January 14, 2026
PubMed

Insights

The study reveals a link between EPHA3 and YAP1 in prostate tumors, showing their combined role in cancer progression. Targeting this YAP1-EPHA3 axis may offer new therapeutic strategies for cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The transcriptional coregulator YAP1 and receptor tyrosine kinase EPHA3 are vital in cellular processes like development and cancer.
  • While their individual functions are known, their combined roles in cancer progression are not well understood.

Purpose of the Study:

  • To investigate the cooperative functions of EPHA3 and YAP1 in human prostate tumor tissues and cell models.
  • To explore the YAP1-EPHA3 axis as a potential therapeutic target in prostate cancer.

Main Methods:

  • Integrated transcriptomic and immunological analyses of human prostate tumor tissues.
  • In vitro studies using EPHA3 knockout and depletion in cell models.
  • Bioinformatics analysis of gene expression signatures.

Main Results:

  • A significant positive correlation was found between YAP1 and EPHA3 expression, associated with tumor progression.
  • EPHA3 knockout reduced proliferation and increased sensitivity to enzalutamide and CA3.
  • EPHA3 depletion affected RHOA, ERK, EMT, and cancer stem cell programs, reducing migration and invasion.

Conclusions:

  • The YAP1-EPHA3 axis is a key mediator of cell survival, plasticity, and tumor progression in prostate cancer.
  • This axis represents a promising therapeutic target for novel cancer drugs.

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