Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Jesse Bakke, William C. Wright, Anthony E. Zamora, Peter Oladimeji, Jeremy Chase Crawford, Christopher T. Brewer, Robert J. Autry, William E. Evans, Paul G. Thomas, Taosheng Chen

ABSTRACT

BACKGROUND: Despite its relatively low incidence, pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths because of the aggressive growth/metastasis of the tumor, the lack of early symptoms, and the poor treatment options. Basic research to identify potential therapeutic targets for PDAC is greatly needed. METHODS: We used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line. We validated the top hits with follow-up siRNA screens, using the HPNE, HPAF-II, AsPC-1, and Mia PaCa-2 cell lines. RESULTS: The PSMA6 gene was an identified candidate hit after the CRISPR screen, siRNA validation screen, and siRNA deconvolution screen. Spheroid formation assays and flow cytometry analysis showed that PSMA6 is critical for survival in many pancreatic ductal carcinoma cell models. Lastly, as PSMA6 protein is a proteosomal subunit of the 20S core complex, we showed that bortezomib, a proteasome inhibitor, was especially toxic in PANC-1 cells. CONCLUSIONS: Further study of PSMA6 and the proteasome subunit that it encodes, along with other hits identified in our CRISPR screens, may provide valuable insights into potential therapeutic targets for PDAC. More... »

PAGES

253

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12885-019-5455-1

    DOI

    http://dx.doi.org/10.1186/s12885-019-5455-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112926597

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30898113


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