| First Author | Wu Z | Year | 2023 |
| Journal | Dev Cell | Volume | 58 |
| Issue | 23 | Pages | 2684-2699.e6 |
| PubMed ID | 37944525 | Mgi Jnum | J:343274 |
| Mgi Id | MGI:7565218 | Doi | 10.1016/j.devcel.2023.10.006 |
| Citation | Wu Z, et al. (2023) CLMP is a tumor suppressor that determines all-trans retinoic acid response in colorectal cancer. Dev Cell 58(23):2684-2699.e6 |
| abstractText | CAR-like membrane protein (CLMP) is a tight junction-associated protein whose mutation is associated with congenital short bowel syndrome (CSBS), but its functions in colorectal cancer (CRC) remain unknown. Here, we demonstrate that CLMP is rarely mutated but significantly decreased in CRC patients, and its deficiency accelerates CRC tumorigenesis, growth, and resistance to all-trans retinoic acid (ATRA). Mechanistically, CLMP recruits beta-catenin to cell membrane, independent of cadherin proteins. CLMP-mediated beta-catenin translocation inactivates Wnt(Wingless and INT-1)/beta-catenin signaling, thereby suppressing CRC tumorigenesis and growth in Apc(Min/+), azoxymethane/dextran sodium sulfate (AOM/DSS), and orthotopic CRC mouse models. As a direct target of Wnt/beta-catenin, cytochrome P450 hydroxylase A1 (CYP26A1)-an enzyme that degrades ATRA to a less bioactive retinoid-is upregulated by CLMP deficiency, resulting in ATRA-resistant CRC that can be reversed by administering CYP26A1 inhibitor. Collectively, our data identify the anti-CRC role of CLMP and suggest that CYP26A1 inhibitor enable to boost ATRA's therapeutic efficiency. |
