{"id":22532,"date":"2021-01-12T08:54:07","date_gmt":"2021-01-12T13:54:07","guid":{"rendered":"https:\/\/www.bu.edu\/chemistry\/?p=22532"},"modified":"2021-01-12T08:54:07","modified_gmt":"2021-01-12T13:54:07","slug":"vanessa-stahl-class-of-21","status":"publish","type":"post","link":"https:\/\/www.bu.edu\/chemistry\/2021\/01\/12\/vanessa-stahl-class-of-21\/","title":{"rendered":"Vanessa Stahl (Class of &#8217;21)"},"content":{"rendered":"<p><a href=\"https:\/\/doi.org\/10.1039\/D0MO00009D\">\u03b2-Catenin\/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma<\/a><\/p>\n<p style=\"text-align: justify;\"><span>Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose activity is upregulated in &gt;80% OSCC. Current anti-EGFR therapy relies on the use of cetuximab, a monoclonal antibody against EGFR, although it has had only a limited response in patients. Here, we uncover a novel mechanism regulating EGFR activity, identifying a role of the nuclear branch of the Wnt\/\u03b2-catenin signaling pathway, the \u03b2-catenin\/CBP axis, in control of post-translational modification of\u00a0<\/span><em>N<\/em><span>-glycans on the EGFR. Genomic and structural analyses reveal that \u03b2-catenin\/CBP signaling represses fucosylation on the antennae of\u00a0<\/span><em>N<\/em><span>-linked glycans on EGFR. By employing nUPLC-MS\/MS, we determined that malignant human OSCC cells harbor EGFR with a paucity of\u00a0<\/span><em>N<\/em><span>-glycan antennary fucosylation, while indolent cells display higher levels of fucosylation at sites N420 and N579. Additionally, treatment with either ICG-001 or E7386, which are both small molecule inhibitors of \u03b2-catenin\/CBP signaling, leads to increased transcriptional expression of fucosyltransferases FUT2 and FUT3, with a concomitant increase in EGFR\u00a0<\/span><em>N<\/em><span>-glycan antennary fucosylation. In order to discover which fucosylated glycan epitopes are involved in the observed effect, we performed in-depth characterization of multiply-fucosylated\u00a0<\/span><em>N<\/em><span>-glycans\u00a0<\/span><em>via<\/em><span>\u00a0tandem mass spectrometry analysis of the EGFR tryptic glycopeptides. Data are available\u00a0<\/span><em>via<\/em><span>\u00a0ProteomeXchange with identifier PXD017060. We propose that \u03b2-catenin\/CBP signaling promotes EGFR oncogenic activity in OSCC by inhibiting its\u00a0<\/span><em>N<\/em><span>-glycan antennary fucosylation through transcriptional repression of FUT2 and FUT3.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>\u03b2-Catenin\/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose [&hellip;]<\/p>\n","protected":false},"author":10766,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[9283,9297,9275,9274],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/posts\/22532"}],"collection":[{"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/users\/10766"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/comments?post=22532"}],"version-history":[{"count":1,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/posts\/22532\/revisions"}],"predecessor-version":[{"id":22533,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/posts\/22532\/revisions\/22533"}],"wp:attachment":[{"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/media?parent=22532"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/categories?post=22532"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bu.edu\/chemistry\/wp-json\/wp\/v2\/tags?post=22532"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}