Related Experiment Video

Updated: Sep 8, 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

20.0K

Integrated screens uncover a cell surface tumor suppressor gene KIRREL involved in Hippo pathway

Chao Wang1, Xu Feng1, Dan Su1

  • 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 2022
PubMed

Insights

Loss of cell surface protein Kirre1 (KIRREL) promotes tumor growth by inactivating the Hippo pathway. This study reveals KIRREL as a novel tumor suppressor and highlights CRISPR screening for cell surface protein discovery.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Cell surface proteins are crucial for biological processes and cancer development.
  • They are valuable markers for cell identity and drug targets.
  • Comprehensive functional analysis of cell surface proteins is limited.

Purpose of the Study:

  • To functionally analyze cell surface proteins using in vivo CRISPR screens.
  • To identify cell surface proteins affecting tumor survival and proliferation.
  • To uncover novel cell surface tumor suppressors and their mechanisms.

Main Methods:

  • Designed a de novo library targeting cell surface proteins.
  • Performed in vivo CRISPR screens to assess protein function in tumors.
  • Utilized a Hippo pathway reporter for enrichment screening.
  • Conducted biochemical assays to determine protein interactions.

Main Results:

  • Loss of Kirre1 (KIRREL) significantly promoted tumor growth in vivo.
  • KIRREL was identified through CRISPR screens targeting the Hippo pathway.
  • KIRREL directly binds to SAV1, activating the Hippo tumor suppressor pathway.

Conclusions:

  • Kirre1 acts as a cell surface tumor suppressor.
  • KIRREL regulates tumor growth via the Hippo pathway.
  • CRISPR screening is a powerful approach for cell surface protein discovery in cancer research.
Keywords:
CRISPRHippoKIRRELSAV1integrated screens

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