Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen
- King, LE; Zhang, HH; Gould, CM; Thomas, DW; Whitehead, LW; Simpson, KJ; Burgess, AW; Faux, MC;
Publication Year 2020, Volume 15, Issue #10, Page e0240746
- Journal Title
- PLoS One
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- Advanced Technology And Biology; Personalised Oncology
- Publisher's Version
- Open Access at Publisher's Site
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:05:25Last Modified: 2021-03-02 11:03:44