Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis

Cell
Sidi ChenPhillip A Sharp

Abstract

Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were found to target a small set of genes, suggesting that specific loss-of-function mutations drive tumor growth and metastasis. Individual sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the primary screen dramatically accelerate metastasis. In all of these experiments, the effect of mutations on primary tumor growth positively correlates with the development of metastases. Our study demonstrates Cas9-based screening as a robust method to systematically assay gene phenotypes in cancer evolution in vivo.

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K TanoS Mitra
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Mar 24, 2007·Science·Rodolphe BarrangouPhilippe Horvath
Dec 23, 2008·Cancer Genetics and Cytogenetics·Emilia Jesien-LewandowiczRadzisław Kordek
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Mar 25, 2009·Nature Reviews. Cancer·Don X NguyenJoan Massagué
Nov 12, 2009·Genes & Development·Madhu S KumarTyler Jacks
Jan 25, 2011·Nature Reviews. Cancer·Giulio FranciaRobert S Kerbel
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Aug 5, 2011·Nucleic Acids Research·Rimantas SapranauskasVirginijus Siksnys
Oct 18, 2011·Cell·Scott Valastyan, Robert A Weinberg
Jun 30, 2012·Science·Martin JinekEmmanuelle Charpentier
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Giedrius GasiunasVirginijus Siksnys
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Apr 2, 2013·Cell·Levi A Garraway, Eric S Lander
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 9, 2013·RNA Biology·Krzysztof ChylinskiEmmanuelle Charpentier
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Oct 19, 2013·Cancer Cell·Sakari Vanharanta, Joan Massagué
Dec 18, 2013·Science·Tim WangEric S Lander
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Dec 18, 2013·Biochimica Et Biophysica Acta·Concetta SchianoClaudio Napoli
Jan 10, 2014·Biomicrofluidics·Jaehoon ChungHakho Lee
Apr 15, 2014·Nucleic Acids Research·Krzysztof ChylinskiEugene V Koonin
May 3, 2014·Genes & Development·Sidi ChenPhillip A Sharp
Jun 24, 2014·Cell·Diane D ShaoWilliam C Hahn
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Aug 1, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 6, 2014·Experimental & Molecular Medicine·Zhenshun ChengLi Zhang
Sep 30, 2014·Cell·Randall J PlattFeng Zhang
Oct 14, 2014·Cell·Luke A GilbertJonathan S Weissman

❮ Previous
Next ❯

Citations

Feb 18, 2016·BMC Biotechnology·C LiescheJ Beaudouin
Sep 22, 2015·International Journal of Molecular Sciences·Raul Torres-Ruiz, Sandra Rodriguez-Perales
Dec 3, 2015·Expert Opinion on Biological Therapy·Apollo D Kacsinta, Steven F Dowdy
Jan 3, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Adi F GazdarJohn D Minna
Mar 8, 2016·Trends in Cancer·Kamil A LipinskiMarco Gerlinger
Jan 30, 2016·Nature Reviews. Cancer·Emmy D G FleurenRoger J Daly
Nov 7, 2015·Proceedings of the National Academy of Sciences of the United States of America·Narayana YeddulaInder M Verma
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Claire M FaltermeierOwen N Witte
Nov 1, 2015·Genome Biology·Peng JiangX Shirley Liu
Oct 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Julia WeberRoland Rad
Dec 25, 2015·Endocrine Journal·Izuho Hatada, Takuro Horii
Mar 2, 2016·Biochemical and Biophysical Research Communications·Michela Deleidi, Cong Yu
Feb 13, 2016·Trends in Cancer·Florian L MullerRonald A DePinho
Sep 17, 2015·Nature·Matthew C CanverDaniel E Bauer
Nov 28, 2015·Genome Biology·Daniel B Graham, David E Root
Sep 19, 2015·Angewandte Chemie·Marion Kirchner, Sabine Schneider
Apr 1, 2016·Future Oncology·Gustav van NiekerkAnna-Mart Engelbrecht
Oct 7, 2015·Frontiers in Genetics·Alexander Agrotis, Robin Ketteler
Oct 4, 2015·Trends in Molecular Medicine·Lukas E Dow
Jul 3, 2015·Evolutionary Applications·Britt Koskella
Jun 27, 2015·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rebecca E McIntyreDavid J Adams
Apr 14, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Deboki ChakravartiWilson W Wong
Jul 3, 2015·Cell & Bioscience·Sean M RiordanShui Qing Ye
Jun 5, 2015·Nature Reviews. Cancer·Francisco J Sánchez-Rivera, Tyler Jacks
May 8, 2015·Nature Medicine·Stephen E GouldFrederic J de Sauvage
May 18, 2016·Trends in Parasitology·Jin-Lei WangXing-Quan Zhu
May 18, 2016·Progress in Retinal and Eye Research·Sandy S C HungAlex W Hewitt
Feb 26, 2016·Annual Review of Pathology·James T Neal, Calvin J Kuo
May 26, 2016·Seminars in Cell & Developmental Biology·Krysta L EngelDaniel Savic
Jun 5, 2016·Analytical Biochemistry·Neville E Sanjana
Dec 18, 2015·Journal of Medical Genetics·Hui-Ying XueXiao-Jie Lu
May 6, 2016·Annual Review of Chemical and Biomolecular Engineering·Christopher E Nelson, Charles A Gersbach
Jun 17, 2016·Current Opinion in Immunology·Kai W Wucherpfennig, Adam Nr Cartwright
Jun 22, 2016·Proceedings of the National Academy of Sciences of the United States of America·Christian J BraunMichael T Hemann
Jun 23, 2016·Briefings in Functional Genomics·Xiaolong QiGuoxin Li
Jun 28, 2016·Briefings in Functional Genomics·Raul Torres-Ruiz, Sandra Rodriguez-Perales
Jun 28, 2016·Biomarkers in Medicine·Xiaoying JiangQilan Ning

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

CRISPR in Cancer

CRISPR-Cas system enables the editing of genes to create or correct mutations. Given that genome instability and mutation is one of the hallmarks of cancer, the CRISPR-Cas system is being explored to genetically alter and eliminate cancer cells. Here is the latest research.