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The Hippo pathway transcriptional co-activator, YAP, is an ovarian cancer oncogene

X Zhang1, J George, S Deb

  • 1Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Oncogene
|February 15, 2011
PubMed

Insights

The Salvador-Warts-Hippo (SWH) pathway regulates tissue growth. In ovarian cancer, YAP, a key protein in this pathway, promotes tumor growth and chemoresistance, indicating SWH pathway as a therapeutic target.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • The Salvador-Warts-Hippo (SWH) pathway is a conserved signaling cascade that inhibits tissue growth.
  • In mammals, the SWH pathway restricts tissue growth by limiting the nuclear entry and expression of the transcriptional co-activator Yes-associated protein (YAP).
  • While SWH pathway alterations are implicated in human cancers, their specific role in tumorigenesis remains unclear.

Purpose of the Study:

  • To investigate the role of YAP in ovarian cancer development and chemoresistance.
  • To determine the prognostic significance of nuclear YAP expression in ovarian cancer patients.
  • To explore the therapeutic potential of targeting the SWH pathway in ovarian cancer.

Main Methods:

  • Ovarian cancer cell lines were utilized to assess YAP's effect on transformed phenotypes and chemotherapeutic resistance.
  • A cohort of 268 invasive epithelial ovarian cancer samples was analyzed for nuclear YAP expression.
  • Immunohistochemistry was employed to correlate YAP levels with patient survival and histotype.

Main Results:

  • YAP enhances the transformed phenotype of ovarian cancer cells and confers resistance to common chemotherapeutic agents.
  • High nuclear YAP expression is significantly correlated with poor patient prognosis in invasive epithelial ovarian cancer.
  • This correlation is particularly pronounced in clear cell ovarian tumors, irrespective of cancer stage.

Conclusions:

  • YAP derepression contributes to the pathogenesis of ovarian clear cell carcinoma.
  • The SWH pathway represents a promising therapeutic target for ovarian cancer, especially clear cell subtypes.
  • Targeting YAP or upstream SWH pathway components may offer new treatment strategies for ovarian cancer.

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