Regulation of Wnt receptor activity: Implications for therapeutic development in colon cancer.
J Biol Chem
; 296: 100782, 2021.
Article
en En
| MEDLINE
| ID: mdl-34000297
ABSTRACT
Hyperactivation of Wnt/ß-catenin (canonical) signaling in colorectal cancers (CRCs) was identified in the 1990s. Most CRC patients have mutations in genes that encode components of the Wnt pathway. Inactivating mutations in the adenomatous polyposis coli (APC) gene, which encodes a protein necessary for ß-catenin degradation, are by far the most prevalent. Other Wnt signaling components are mutated in a smaller proportion of CRCs; these include a FZD-specific ubiquitin E3 ligase known as ring finger protein 43 that removes FZDs from the cell membrane. Our understanding of the genetic and epigenetic landscape of CRC has grown exponentially because of contributions from high-throughput sequencing projects such as The Cancer Genome Atlas. Despite this, no Wnt modulators have been successfully developed for CRC-targeted therapies. In this review, we will focus on the Wnt receptor complex, and speculate on recent discoveries about ring finger protein 43regulating Wnt receptors in CRCs. We then review the current debate on a new APC-Wnt receptor interaction model with therapeutic implications.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias del Colon
/
Receptores Wnt
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos