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dc.contributor.authorPandey, Ritu
dc.contributor.authorZhou, Muhan
dc.contributor.authorIslam, Shariful
dc.contributor.authorChen, Baowei
dc.contributor.authorBarker, Natalie K
dc.contributor.authorLanglais, Paul
dc.contributor.authorSrivastava, Anup
dc.contributor.authorLuo, Moulun
dc.contributor.authorCooke, Laurence S
dc.contributor.authorWeterings, Eric
dc.contributor.authorMahadevan, Daruka
dc.date.accessioned2020-01-29T20:20:54Z
dc.date.available2020-01-29T20:20:54Z
dc.date.issued2019-12-04
dc.identifier.citationPandey, R., Zhou, M., Islam, S. et al. Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target. Sci Rep 9, 18347 (2019). https://doi.org/10.1038/s41598-019-54545-9en_US
dc.identifier.issn2045-2322
dc.identifier.pmid31797958
dc.identifier.doi10.1038/s41598-019-54545-9
dc.identifier.urihttp://hdl.handle.net/10150/636770
dc.description.abstractWe investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and correlations. A CRISPR/Cas9 Knockout (KO) of CEACAM6 in PDA cell line for quantitative proteomics, mitochondrial bioenergetics and tumor growth in mice were conducted. We found CEACAM6 is over-expressed in primary and metastatic basal and classical PDA subtypes. Highest levels are in classical activated stroma subtype. CEACAM6 over-expression is universally a poor prognostic marker in KRAS mutant and wild type PDA. High CEACAM6 expression is associated with low cytolytic T-cell activity in both basal and classical PDA subtypes and correlates with low levels of T-REG markers. In HPAF-II cells knockout of CEACAM6 alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport and autophagy. CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity. HPAF-II CEACAM6-/- cells are growth suppressed by >65% vs. wild type in mice bearing tumors. CEACAM6, a key regulator affects several hallmarks of PDA including the fibrotic reaction, immune regulation, energy metabolism and is a novel therapeutic target in PDA.en_US
dc.description.sponsorshipUniversity of Arizona Cancer Center Cancer Center Support Grant [P30 CA023074]; NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [2P30 CA023074]en_US
dc.language.isoenen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.rightsCopyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.titleCarcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic targeten_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Canc Ctren_US
dc.contributor.departmentUniv Arizona, Dept Cellular & Mol Meden_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Meden_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Radiat Oncolen_US
dc.identifier.journalSCIENTIFIC REPORTSen_US
dc.description.noteOpen access journalen_US
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_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleScientific reports
refterms.dateFOA2020-01-29T20:20:55Z


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