Abstract
Abstract Despite advancements in the field, the 5 year survival rate of Head and Neck Squamous Cell Carcinoma (HNSCC) still hovers at 60%. In a quest for novel therapy targets for this disease, we performed an extensive and comprehensive quantitative phosphoproteomics scan on 10 HNSCC patient derived xenografts (PDXs) in order to find dysregulated phosphoproteins. DCLK1 is hyperphosphorylated but not over expressed in most of the HNSCC derived PDXs. DCLK1 has been shown to regulate epithelial-to-mesenchymal transition (EMT) as well as serving as a cancer stem cell marker in colon and pancreas cancer. DCLK1 is also associated with bad prognosis in colon, renal and oropharyngeal cancers. We performed a comprehensive transcriptome-based computational analysis on hundreds of HNSCC patients from TCGA and GEO databases. While our results confirm the role of DCLK1 in regulating EMT and focal adhesion kinase (FAK) mediated integrin signaling, we found that high DCLK1 expression also correlates with NOTCH pathway signaling signatures in HNSCC. We have selected 5 cell HNSCC cell lines (JHU-011, JHU-022, JHU-029, FaDu and Cal29) that express DCLK1, and inhibited DCLK1 with LRRK2-in1 inhibitor and siRNA. DCLK1 inhibition resulted in substantially decreased proliferation, migration, and colony formation. Furthermore, these effects paralleled downregulation NOTCH1 signaling in all cell lines tested. Overall, our results demonstrate the novel role of DCLK1 in regulating the NOTCH signaling network and suggest its potential as a therapeutic target in HNSCC. Citation Format: Esther Channah Broner, Tejaswini Subbannayya, Jayshree Advani, Alex Zhavoronkov, Artem Artemov, Ivan Ozerov, Ido Sloma, Harsha Gowda, David Sidransky, Eugene Izumchenko, Aditi Chatterjee. Doublecortin-like kinase 1 (DCLK1) correlates with Notch pathway signaling, controls metastatic characteristics in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4512.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
