| First Author | Huels DJ | Year | 2015 |
| Journal | EMBO J | Volume | 34 |
| Issue | 18 | Pages | 2321-33 |
| PubMed ID | 26240067 | Mgi Jnum | J:226570 |
| Mgi Id | MGI:5697770 | Doi | 10.15252/embj.201591739 |
| Citation | Huels DJ, et al. (2015) E-cadherin can limit the transforming properties of activating beta-catenin mutations. EMBO J 34(18):2321-33 |
| abstractText | Wnt pathway deregulation is a common characteristic of many cancers. Only colorectal cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of the pancreas) have activating mutations in beta-catenin (CTNNB1). We have compared the dynamics and the potency of beta-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of beta-catenin took much longer to achieve Wnt deregulation and acquire a crypt-progenitor cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of beta-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of beta-catenin mutation to differentially transform the SI versus the colon correlated with higher expression of E-cadherin and a higher number of E-cadherin:beta-catenin complexes at the membrane. Reduction in E-cadherin synergised with an activating mutation of beta-catenin resulting in a rapid CPC phenotype within the SI and colon. Thus, there is a threshold of beta-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated beta-catenin. |
