MUC1 stimulates EGFR expression and function in endometrial cancer

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dc.citation.journalTitleOncotargeten_US
dc.contributor.authorEngel, Brian J.en_US
dc.contributor.authorBowser, Jessica L.en_US
dc.contributor.authorBroaddus, Russell R.en_US
dc.contributor.authorCarson, Daniel D.en_US
dc.date.accessioned2016-06-27T17:03:14Zen_US
dc.date.available2016-06-27T17:03:14Zen_US
dc.date.issued2016en_US
dc.description.abstractThe current standard of care for endometrial cancer patients involves hysterectomy with adjuvant radiation and chemotherapy, with no effective treatment for advanced and metastatic disease. MUC1 is a large, heavily glycosylated transmembrane protein that lubricates and protects cell surfaces and increases cellular signaling through the epidermal growth factor receptor (EGFR). We show for the first time that MUC1 stimulates EGFR expression and function in endometrial cancer. siRNA knockdown and CRISPR/Cas knockout of MUC1 reduced EGFR gene expression, mRNA, protein levels and signaling. MUC1 bound strongly to two regions of the EGFR promoter: -627/-511 and -172/-64. MUC1 knockout also reduced EGFR-dependent proliferation in two dimensional culture, as well as growth and survival in three dimensional spheroid cultures. MUC1 knockout cells were more sensitive to the EGFR inhibitor, lapatinib. Finally, MUC1 and EGFR co-expression was associated with increased cellular proliferation in human endometrial tumors. These data demonstrate the importance of MUC1-driven EGFR expression and signaling and suggest dual-targeted therapies may provide improved response for endometrial tumors.en_US
dc.identifier.citationEngel, Brian J., Bowser, Jessica L., Broaddus, Russell R., et al.. "MUC1 stimulates EGFR expression and function in endometrial cancer." <i>Oncotarget,</i> (2016) Impact Journals, LLC: http://dx.doi.org/10.18632/oncotarget.8743.en_US
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.8743en_US
dc.identifier.urihttps://hdl.handle.net/1911/90593en_US
dc.language.isoengen_US
dc.publisherImpact Journals, LLCen_US
dc.rightsAll content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordEGFRen_US
dc.subject.keywordMUC1en_US
dc.subject.keywordendometrial canceren_US
dc.titleMUC1 stimulates EGFR expression and function in endometrial canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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