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

Chao Wang, Xu Feng, Dan Su, Zhen Chen, Shimin Wang, Mengfan Tang, Min Huang, Litong Nie, Huimin Zhang, Siting Li, Ling Yin, Randy L. Johnson, Traver Hart, Junjie Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Cell surface proteins play essential roles in various biological processes and are highly related to cancer development. They also serve as important markers for cell identity and targets for pharmacological intervention. Despite their great potentials in biomedical research, comprehensive functional analysis of cell surface proteins remains scarce. Here, with a de novo designed library targeting cell surface proteins, we performed in vivo CRISPR screens to evaluate the effects of cell surface proteins on tumor survival and proliferation. We found that Kirrel1 loss markedly promoted tumor growth in vivo. Moreover, KIRREL was significantly enriched in a separate CRISPR screen based on a specific Hippo pathway reporter. Further studies revealed that KIRREL binds directly to SAV1 to activate the Hippo tumor suppressor pathway. Together, our integrated screens reveal a cell surface tumor suppressor involved in the Hippo pathway and highlight the potential of these approaches in biomedical research.

Original languageEnglish (US)
Article numbere2121779119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - Jun 21 2022


  • Hippo
  • integrated screens
  • SAV1

ASJC Scopus subject areas

  • General


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