APC controls Wnt-induced ß-catenin destruction complex recruitment in human colonocytes.
Sci Rep
; 10(1): 2957, 2020 02 19.
Article
em En
| MEDLINE
| ID: mdl-32076059
ABSTRACT
Wnt/ß-catenin signaling is essential for intestinal homeostasis and is aberrantly activated in most colorectal cancers (CRC) through mutation of the tumor suppressor Adenomatous Polyposis Coli (APC). APC is an essential component of a cytoplasmic protein complex that targets ß-catenin for destruction. Following Wnt ligand presentation, this complex is inhibited. However, a role for APC in this inhibition has not been shown. Here, we utilized Wnt3a-beads to locally activate Wnt co-receptors. In response, the endogenous ß-catenin destruction complex reoriented toward the local Wnt cue in CRC cells with full-length APC, but not if APC was truncated or depleted. Non-transformed human colon epithelial cells displayed similar Wnt-induced destruction complex localization which appeared to be dependent on APC and less so on Axin. Our results expand the current model of Wnt/ß-catenin signaling such that in response to Wnt, the ß-catenin destruction complex (1) maintains composition and binding to ß-catenin, (2) moves toward the plasma membrane, and (3) requires full-length APC for this relocalization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína da Polipose Adenomatosa do Colo
/
Células Epiteliais
/
Beta Catenina
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Complexo de Sinalização da Axina
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Proteína Wnt3A
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos