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dc.contributor.authorKing, LE
dc.contributor.authorZhang, H-H
dc.contributor.authorGould, CM
dc.contributor.authorThomas, DW
dc.contributor.authorWhitehead, LW
dc.contributor.authorSimpson, KJ
dc.contributor.authorBurgess, AW
dc.contributor.authorFaux, MC
dc.date.accessioned2020-11-17T04:06:19Z
dc.date.available2020-11-17T04:06:19Z
dc.date.issued2020-10-15
dc.identifierpii: PONE-D-20-23014
dc.identifier.citationKing, L. E., Zhang, H. -H., Gould, C. M., Thomas, D. W., Whitehead, L. W., Simpson, K. J., Burgess, A. W. & Faux, M. C. (2020). Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen. PLOS ONE, 15 (10), https://doi.org/10.1371/journal.pone.0240746.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/251701
dc.description.abstractTruncating mutations in the tumour suppressor gene APC occur frequently in colorectal cancers and result in the deregulation of Wnt signalling as well as changes in cell-cell adhesion. Using quantitative imaging based on the detection of membrane-associated E-cadherin, we undertook a protein coding genome-wide siRNA screen to identify genes that regulate cell surface E-cadherin in the APC-defective colorectal cancer cell line SW480. We identified a diverse set of regulators of E-cadherin that offer new insights into the regulation of cell-cell adhesion, junction formation and genes that regulate proliferation or survival of SW480 cells. Among the genes whose depletion promotes membrane-associated E-cadherin, we identified ZEB1, the microRNA200 family, and proteins such as a ubiquitin ligase UBE2E3, CDK8, sorting nexin 27 (SNX27) and the matrix metalloproteinases, MMP14 and MMP19. The screen also identified 167 proteins required for maintaining E-cadherin at cell-cell adherens junctions, including known junctional proteins, CTNND1 and CTNNA1, as well as signalling enzymes, DUSP4 and MARK2, and transcription factors, TEAD3, RUNX2 and TRAM2. A better understanding of the post-translational regulation of E-cadherin provides new opportunities for restoring cell-cell adhesion in APC-defective cells.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGenes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0240746
melbourne.affiliation.departmentSurgery (RMH)
melbourne.source.titlePLoS One
melbourne.source.volume15
melbourne.source.issue10
melbourne.source.pagese0240746-
dc.rights.licenseCC BY
melbourne.elementsid1468936
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561197
melbourne.contributor.authorWhitehead, Lachlan
melbourne.contributor.authorBurgess, Antony
melbourne.contributor.authorSimpson, Kaylene
melbourne.contributor.authorKing, Lauren
melbourne.contributor.authorFaux, Maree
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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