@article{c62cf17ce4d64e9a834b1f0cf7fc3ff2,
title = "Integrated screens uncover a cell surface tumor suppressor gene KIRREL involved in Hippo pathway",
abstract = "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.",
keywords = "CRISPR, Hippo, integrated screens, KIRREL, SAV1",
author = "Chao Wang and Xu Feng and Dan Su and Zhen Chen and Shimin Wang and Mengfan Tang and Min Huang and Litong Nie and Huimin Zhang and Siting Li and Ling Yin and Johnson, {Randy L.} and Traver Hart and Junjie Chen",
note = "Funding Information: We thank all members of the Chen laboratory for their help and constructive discussion. We thank Wenqi Wang (University of California, Irvine) for providing SAV1-KO cells. We thank Xuelian Luo (UT Southwestern) for providing SAV1-related plasmids. We thank Boyi Gan (MD Anderson Cancer Center) for providing pBabe-Cre-puro plasmid. We thank MD Anderson{\textquoteright}s Science Park NGS Facility for their help with CRISPR library NGS sequencing (supported by MD Anderson{\textquoteright}s NIH Cancer Center Support Grant, P30CA016672). We thank Sunita Patterson (Research Medical Library, MD Anderson) for providing editing service. This work was supported in part by institutional funds and the Pamela and Wayne Garrison Distinguished Chair in Cancer Research. J.C. also received support from CPRIT (RP160667, RP180813) and NIH/the National Cancer Institute (CA193124, CA210929, CA216911, and CA216437). T.H. received support from NIH (R35GM130119) and is an Andrew Sabin Family Fellow and a CPRIT Scholar in Cancer Research. Funding Information: ACKNOWLEDGMENTS. We thank all members of the Chen laboratory for their help and constructive discussion. We thank Wenqi Wang (University of California, Irvine) for providing SAV1-KO cells. We thank Xuelian Luo (UT Southwestern) for providing SAV1-related plasmids. We thank Boyi Gan (MD Anderson Cancer Center) for providing pBabe-Cre-puro plasmid. We thank MD Anderson{\textquoteright}s Science Park NGS Facility for their help with CRISPR library NGS sequencing (supported by MD Anderson{\textquoteright}s NIH Cancer Center Support Grant, P30CA016672). We thank Sunita Patterson (Research Medical Library, MD Anderson) for providing editing service. This work was supported in part by institutional funds and the Pamela and Wayne Garrison Distinguished Chair in Cancer Research. J.C. also received support from CPRIT (RP160667, RP180813) and NIH/the National Cancer Institute (CA193124, CA210929, CA216911, and CA216437). T.H. received support from NIH (R35GM130119) and is an Andrew Sabin Family Fellow and a CPRIT Scholar in Cancer Research. Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s). Published by PNAS.",
year = "2022",
month = jun,
day = "21",
doi = "10.1073/pnas.2121779119",
language = "English (US)",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "25",
}