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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance

Dong-Yu Wang1, Ya-Nan Wu1, Jun-Qi Huang1

  • 1Department of Orthopaedics and Rehabilitation, PLA General Hospital, Fuxing Rd 28, Beijing, 100853, P. R. China.

Chinese Journal of Cancer
|May 22, 2016
PubMed
Abstract

Insights

The Hippo/yes-associated protein (YAP) pathway drives osteosarcoma chemoresistance. Targeting YAP may improve treatment outcomes for this bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Osteosarcoma, a common childhood bone cancer, presents a poor prognosis in 20-30% of patients due to chemoresistance.
  • The Hippo/yes-associated protein (YAP) signaling pathway is implicated in tumor chemoresistance, but its role in osteosarcoma remains unexplored.

Purpose of the Study:

  • To investigate the role of the Hippo/YAP signaling pathway in osteosarcoma chemoresistance.
  • To identify potential therapeutic targets within this pathway for overcoming chemoresistance.

Main Methods:

  • Assessed proliferation and chemosensitivity of osteosarcoma cells with altered YAP expression (overexpression and knockdown) using cell viability assays and flow cytometry.
  • Utilized western blotting and real-time PCR to examine Hippo/YAP pathway modulation in response to chemotherapeutic agents (methotrexate, doxorubicin).

Main Results:

  • Methotrexate and doxorubicin treatment led to increased Mammalian sterile 20-like kinase 1 (MST1) degradation and decreased large tumor suppressor kinase 1/2 (LATS1/2) protein levels.
  • These changes resulted in enhanced YAP activation and nuclear translocation, correlating with increased proliferation and chemoresistance in MG63 osteosarcoma cells.

Conclusions:

  • The Hippo/YAP signaling pathway is a key player in the development of osteosarcoma chemoresistance.
  • YAP represents a promising therapeutic target for strategies aimed at reducing chemoresistance in osteosarcoma.
Keywords:
ChemoresistanceDoxorubicinHippoMethotrexateOsteosarcomaYAP

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