E-cadherin can limit the transforming properties of activating ß-catenin mutations.
EMBO J
; 34(18): 2321-33, 2015 Sep 14.
Article
in En
| MEDLINE
| ID: mdl-26240067
ABSTRACT
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 ß-catenin (CTNNB1). We have compared the dynamics and the potency of ß-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of ß-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 ß-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of ß-catenin mutation to differentially transform the SI versus the colon correlated with higher expression of E-cadherin and a higher number of E-cadherinß-catenin complexes at the membrane. Reduction in E-cadherin synergised with an activating mutation of ß-catenin resulting in a rapid CPC phenotype within the SI and colon. Thus, there is a threshold of ß-catenin that is required to drive transformation, and E-cadherin can act as a buffer to sequester mutated ß-catenin.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cadherins
/
Cell Transformation, Neoplastic
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Colonic Neoplasms
/
Beta Catenin
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Wnt Signaling Pathway
/
Mutation
/
Neoplasm Proteins
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2015
Document type:
Article
Affiliation country: