Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the ApcMin model of colorectal cancer
| العنوان: | Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the ApcMin model of colorectal cancer |
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| المؤلفون: | Jeanette Schwarz, Marie Kveiborg, Jacob Samsøe-Petersen, Kim B. Jensen, Gary Thomas, Reidar Albrechtsen, Sarah Louise Dombernowsky |
| المصدر: | Oncotarget Dombernowsky, S L, Schwarz, J, Samsøe-Petersen, J, Albrechtsen, R, Jensen, K B, Thomas, G & Kveiborg, M 2017, ' Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the Apc Min model of colorectal cancer ', OncoTarget, vol. 8, no. 65, pp. 108303-108315 . https://doi.org/10.18632/oncotarget.22661Test |
| بيانات النشر: | Impact Journals LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, PACS-2, Proliferative index, Colorectal cancer, Cell, 03 medical and health sciences, Medicine, Colitis, DSS-induced colitis, ApcMin model, ADAM17, business.industry, Regeneration (biology), General surgery, medicine.disease, Intestinal epithelium, humanities, Epithelium, Colon cancer, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Oncology, colon cancer, Cancer research, Apc model, Stem cell, business, Priority Research Paper |
| الوصف: | // Sarah L. Dombernowsky 1,* , Jeanette Schwarz 1,* , Jacob Samsoe-Petersen 1 , Reidar Albrechtsen 1 , Kim B. Jensen 1,2 , Gary Thomas 3 and Marie Kveiborg 1 1 Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark 2 Novo Nordisk Foundation Center for Stem Cell Biology, University of Copenhagen, Copenhagen, Denmark 3 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA * These authors have contributed equally to this work Correspondence to: Marie Kveiborg, email: // Keywords : DSS-induced colitis; colon cancer; ApcMin model; PACS-2; ADAM17 Received : May 07, 2017 Accepted : October 28, 2017 Published : November 26, 2017 Abstract PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2 -/- mice have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2 in these processes. Specifically, we analyzed the role of Pacs 2-deficiency in a DSS-induced colitis model as well as in the genetic Apc Min colon cancer model. We now report that loss of PACS-2 delays tissue regeneration after colonic injury with little effect on key inflammatory parameters. We did however not observe any apparent effects on tumor formation driven by excessive proliferative signaling downstream from APC-deficiency. Our findings reveal that the role of PACS-2 in regulating ADAM17-mediated shedding is not an obligate requirement for the epithelium to respond to the strong inflammatory or tumorigenic inducers in the models assessed here. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1949-2553 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be09ef4a26613e6f07b9e8ae14421aecTest http://europepmc.org/articles/PMC5752446Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....be09ef4a26613e6f07b9e8ae14421aec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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