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dc.contributor.authorGreenwood, Erin*
dc.contributor.authorMaisel, Sabrina*
dc.contributor.authorEbertz, David*
dc.contributor.authorRuss, Atlantis*
dc.contributor.authorPandey, Ritu*
dc.contributor.authorSchroeder, Joyce*
dc.date.accessioned2017-01-24T00:01:02Z
dc.date.available2017-01-24T00:01:02Z
dc.date.issued2016-09-19
dc.identifier.citationGreenwood, Erin, et al. "Llgl1 prevents metaplastic survival driven by epidermal growth factor dependent migration." Oncotarget 7.38 (2016): 60776-60792.en
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.11320
dc.identifier.urihttp://hdl.handle.net/10150/622116
dc.description.abstractWe have previously demonstrated that Llgl1 loss results in a gain of mesenchymal phenotypes and a loss of apicobasal and planar polarity. We now demonstrate that these changes represent a fundamental shift in cellular phenotype. Llgl1 regulates the expression of multiple cell identity markers, including CD44, CD49f, and CD24, and the nuclear translocation of TAZ and Slug. Cells lacking Llgl1 form mammospheres, where survival and transplantability is dependent upon the Epidermal Growth Factor Receptor (EGFR). Additionally, Llgl1 loss allows cells to grow in soft-agar and maintain prolonged survival as orthotopic transplants in NOD-SCID mice. Lineage tracing and wound healing experiments demonstrate that mammosphere survival is due to enhanced EGF-dependent migration. The loss of Llgl1 drives EGFR mislocalization and an EGFR mislocalization point mutation (P667A) drives these same phenotypes, including activation of AKT and TAZ nuclear translocation. Together, these data indicate that the loss of Llgl1 results in EGFR mislocalization, promoting pre-neoplastic changes.
dc.description.sponsorshipNIH [NIH CA023074, T32CA009213, NIGMS T32 GM008659]; NCI [CCSG P30 CA023074]en
dc.language.isoenen
dc.publisherIMPACT JOURNALS LLCen
dc.relation.urlhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=11320en
dc.rightsAll site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.en
dc.subjectpolarityen
dc.subjectmigrationen
dc.subjectLlgl1en
dc.subjectepidermal growth factor receptoren
dc.subjectTAZen
dc.titleLlgl1 prevents metaplastic survival driven by epidermal growth factor dependent migrationen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Mol & Cellular Biolen
dc.contributor.departmentUniv Arizona, Arizona Canc Ctren
dc.contributor.departmentUniv Arizona, Inst BIO5en
dc.contributor.departmentUniv Arizona, Genet Programen
dc.contributor.departmentUniv Arizona, Canc Biol Programen
dc.contributor.departmentUniv Arizona, Cell & Mol Meden
dc.identifier.journalOncotargeten
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2018-06-12T22:01:22Z
html.description.abstractWe have previously demonstrated that Llgl1 loss results in a gain of mesenchymal phenotypes and a loss of apicobasal and planar polarity. We now demonstrate that these changes represent a fundamental shift in cellular phenotype. Llgl1 regulates the expression of multiple cell identity markers, including CD44, CD49f, and CD24, and the nuclear translocation of TAZ and Slug. Cells lacking Llgl1 form mammospheres, where survival and transplantability is dependent upon the Epidermal Growth Factor Receptor (EGFR). Additionally, Llgl1 loss allows cells to grow in soft-agar and maintain prolonged survival as orthotopic transplants in NOD-SCID mice. Lineage tracing and wound healing experiments demonstrate that mammosphere survival is due to enhanced EGF-dependent migration. The loss of Llgl1 drives EGFR mislocalization and an EGFR mislocalization point mutation (P667A) drives these same phenotypes, including activation of AKT and TAZ nuclear translocation. Together, these data indicate that the loss of Llgl1 results in EGFR mislocalization, promoting pre-neoplastic changes.


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