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Details

Autor(en) / Beteiligte
Titel
CAR‐Like Membrane Protein (CLMP) Regulates Intestinal Epithelial Cell Proliferation and Prevents Tumor Growth
Ist Teil von
  • The FASEB journal, 2021-05, Vol.35 (S1), p.n/a, Article fasebj.2021.35.S1.05279
Ort / Verlag
The Federation of American Societies for Experimental Biology
Erscheinungsjahr
2021
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
  • CAR‐Like Membrane Protein (CLMP) is a tight junction‐associated transmembrane protein structurally related to Coxsackie and Adenovirus Receptor (CAR). In humans, loss of function mutations in CLMP have been associated with congenital short bowel syndrome, a rare neonatal intestinal disorder with high mortality, indicating a role in intestinal development. However, the contribution of CLMP in adult gut homeostasis and diseases has not been described. In this study, we investigated the role of CLMP in regulating intestinal epithelial cell (IEC) proliferation using complementary in vivo and in vitro approaches including model human IEC and newly generated mice with inducible intestinal epithelial specific deletion of Clmp (ClmpΔIEC). We observed that Clmp deficiency promotes IEC proliferation in vivo and exacerbates tumor growth in a mouse model of Azoxymethane/Dextran Sulfate Sodium‐induced colitis‐associated cancer. Consistent with these findings, CLMP protein expression was significantly reduced in human colorectal tumor samples. These results were corroborated in vitro in colonoids from ClmpΔIEC mice as well as in human IEC with knockdown of CLMP in which loss of CLMP resulted in increased cell proliferation. By contrast, CLMP overexpression in IEC resulted in significantly reduced cell proliferation. Furthermore, mouse xenograft experiments with CLMP‐deficient tumor cells revealed increased tumor growth, while CLMP overexpressing tumor cells failed to engraft. Mechanistically, CLMP‐dependent regulation of IEC proliferation was determined to be mediated through effects on Akt signaling and beta‐catenin transcriptional activity. Collectively, our findings identify a key role for CLMP in maintenance of intestinal epithelial homeostasis and prevention of tumor development.
Sprache
Englisch
Identifikatoren
ISSN: 0892-6638
eISSN: 1530-6860
DOI: 10.1096/fasebj.2021.35.S1.05279
Titel-ID: cdi_crossref_primary_10_1096_fasebj_2021_35_S1_05279

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