Related Experiment Video

Updated: Jun 28, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

19.8K

Identification of PTPN12 Phosphatase as a Novel Negative Regulator of Hippo Pathway Effectors YAP/TAZ in Breast

Sahar Sarmasti Emami1, Anni Ge1, Derek Zhang1

  • 1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada.

International Journal of Molecular Sciences
|April 13, 2024
PubMed

Insights

Protein tyrosine phosphatases (PTPs) regulate the Hippo pathway, impacting cancer. Researchers identified novel PTPs, including PTPN12, as key regulators of YAP/TAZ activity, offering new therapeutic targets for breast cancer.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • The Hippo pathway is vital for controlling cell proliferation, migration, and apoptosis during tumorigenesis and metastasis.
  • While protein kinases in the Hippo pathway are well-studied, the role of protein phosphatases remains largely unknown.
  • YAP and TAZ are key transcriptional co-activators inhibited by the Hippo pathway's kinase cascade.

Purpose of the Study:

  • To identify protein tyrosine phosphatases (PTPs) that regulate the Hippo signaling pathway.
  • To investigate the role of PTPN12 as a potential regulator of Hippo pathway effectors in breast cancer.

Main Methods:

  • Conducted a gain-of-function screen using a comprehensive PTP library.
  • Employed a LATS kinase biosensor (LATS-BS) and a YAP/TAZ activity reporter (STBS-Luc).
  • Validated findings through subsequent experimental investigations.

Main Results:

  • Identified numerous novel PTPs involved in regulating the Hippo pathway.
  • Validated PTPN12 as a previously unrecognized negative regulator of YAP/TAZ.
  • Demonstrated PTPN12's influence on breast cancer cell proliferation and migration.

Conclusions:

  • Protein tyrosine phosphatases play significant regulatory roles in the Hippo signaling pathway.
  • PTPN12 emerges as a key regulator of oncogenic YAP/TAZ, impacting breast cancer progression.
  • These findings provide insights into breast cancer biology and potential therapeutic avenues targeting PTPs.
Keywords:
Hippo pathwayPTPN12TAZYAPbreast cancercell migrationcell proliferationphosphatasetumor suppressor

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