| First Author | Luissint AC | Year | 2023 |
| Journal | Gastroenterology | PubMed ID | 37716376 |
| Mgi Jnum | J:340886 | Mgi Id | MGI:7531248 |
| Doi | 10.1053/j.gastro.2023.09.012 | Citation | Luissint AC, et al. (2023) CXADR-Like Membrane Protein regulates colonic epithelial cell proliferation and prevents tumor growth. Gastroenterology |
| abstractText | BACKGROUND & AIMS: CXADR-Like Membrane Protein (CLMP) is structurally related to Coxsackie and Adenovirus Receptor. Pathogenic variants in CLMP gene have been associated with congenital short bowel syndrome, implying a role for CLMP in intestinal development. However, the contribution of CLMP to regulating gut development and homeostasis is unknown. METHODS: In this study, we investigated CLMP function in the colonic epithelium using complementary in vivo and in vitro approaches including mice with inducible intestinal epithelial cell (IEC)-specific deletion of CLMP (Clmp(DeltaIEC)), intestinal organoids, IECs with overexpression or loss of CLMP and RNA-seq data from individuals with colorectal cancer (CRC). RESULTS: Loss of CLMP enhanced IEC proliferation and conversely, CLMP overexpression reduced proliferation. Xenograft experiments revealed increased tumor growth in mice implanted with CLMP-deficient colonic tumor cells, while poor engraftment was observed with CLMP-overexpressing cells. Clmp(DeltaIEC) mice showed exacerbated tumor burden in an Azoxymethane/Dextran Sulfate Sodium-induced colonic tumorigenesis model, and CLMP expression was reduced in human CRC samples. Mechanistic studies revealed that CLMP-dependent regulation of IEC proliferation is linked to signaling through mTOR/Akt/beta-catenin pathways. CONCLUSIONS: These results reveal novel insights into CLMP function in the colonic epithelium, highlighting an important role in regulating IEC proliferation, suggesting tumor suppressive function in colon cancer. |
