Article open access publication

Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the Apc Min model of colorectal cancer

Oncotarget, Impact Journals, LLC, ISSN 1949-2553

Volume 5, 0, 2017

DOI:10.18632/oncotarget.22661, Dimensions: pub.1093026076, PMC: PMC5752446, PMID: 29312533,

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) University of Pittsburgh, grid.21925.3d

Description

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 Pacs2-deficiency in a DSS-induced colitis model as well as in the genetic ApcMin 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.

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Dimensions Citation Indicators

Times Cited: 5

Field Citation Ratio (FCR): 1.57

Relative Citation ratio (RCR): 0.14

Open Access Info

Hybrid