Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen.

Autor: King LE; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Zhang HH; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Gould CM; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Thomas DW; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Whitehead LW; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia., Simpson KJ; Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia., Burgess AW; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.; Department of Surgery, RMH, University of Melbourne, Parkville, VIC, Australia., Faux MC; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Oct 15; Vol. 15 (10), pp. e0240746. Date of Electronic Publication: 2020 Oct 15 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0240746
Abstrakt: Truncating 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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