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dc.creatorTikhmyanova, Nadezhda
dc.creatorGolemis, Erica
dc.date.accessioned2023-11-14T17:02:59Z
dc.date.available2023-11-14T17:02:59Z
dc.date.issued2012-07-12
dc.identifier.citationTikhmyanova N, Golemis EA. NEDD9 and BCAR1 Negatively Regulate E-Cadherin Membrane Localization, and Promote E-Cadherin Degradation. PLoS ONE. 2012 Jul 12;6(7):e22102. doi:10.1371/journal.pone.0022102.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/20.500.12613/9213
dc.description.abstractThe Cas scaffolding proteins (NEDD9/HEF1/CAS-L, BCAR1/p130Cas, EFSSIN, and HEPL/CASS4) regulate cell migration, division and survival, and are often deregulated in cancer. High BCAR1 expression is linked to poor prognosis in breast cancer patients, while upregulation of NEDD9 contributes to the metastatic behavior of melanoma and glioblastoma cells. Our recent work knocking out the single Drosophila Cas protein, Dcas, identified a genetic interaction with E-cadherin. As E-cadherin is often downregulated during epithelial-mesenchymal transition (EMT) prior to metastasis, if such an activity was conserved in mammals it might partially explain how Cas proteins promote aggressive tumor behavior. We here establish that Cas proteins negatively regulate E-cadherin expression in human mammary cells. Cas proteins do not affect E-cadherin transcription, but rather, BCAR1 and NEDD9 signal through SRC to promote E-cadherin removal from the cell membrane and lysosomal degradation. We also find mammary tumors arising in MMTV-polyoma virus T-antigen mice have enhanced junctional E-cadherin in a Nedd9−/− background. Cumulatively, these results suggest a new role for Cas proteins in cell-cell adhesion signaling in cancer.
dc.format.extent10 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartPLoS One, Vol. 6
dc.relation.isreferencedbyPublic Library of Science
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBreast cancer
dc.subjectTransfection
dc.subjectBreast tumors
dc.subjectLung and intrathoracic tumors
dc.subjectLysosomes
dc.subjectDrosophila melanogaster
dc.subjectSmall interfering RNA
dc.subjectMembrane proteins
dc.titleNEDD9 and BCAR1 Negatively Regulate E-Cadherin Membrane Localization, and Promote E-Cadherin Degradation
dc.typeText
dc.type.genreJournal article
dc.contributor.groupFox Chase Cancer Center (Temple University)
dc.description.departmentCancer and Cellular Biology
dc.relation.doihttp://dx.doi.org/10.1371/journal.pone.0022102
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.creator.orcidGolemis|0000-0003-3618-3673
dc.temple.creatorTikhmyanova, Nadezhda
dc.temple.creatorGolemis, Erica A.
refterms.dateFOA2023-11-14T17:02:59Z


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