Beta-catenin: a transforming actor on many stages.
Mutations and deletions that result in the stabilization of beta-catenin are frequently found in a number of tumors, including those of the colon, the liver and the ovary, but are less frequently found in breast cancer. To investigate and understand the molecular nature of cell-specific beta-catenin signaling, experimental mouse genetics has been employed extensively. Gain-of-function and loss-of-function mutations have provided evidence that beta-catenin plays essential roles in development and tumorigenesis. Specifically, the Wnt/beta-catenin signaling pathway controls cell fate decisions throughout development, and a unique role in differentiated epithelia has emerged. Not only beta-catenin, but also the activation of other components of this pathway in differentiated mammary epithelium and prostate epithelium of transgenic mice can induce neoplasias and transdifferentiation to squamous metaplasias. This suggests that the Wnt/beta-catenin pathway is dominant over existing differentiation programs and can impose an epidermal fate or neoplasias onto a variety of cell types. Although there is evidence for a contextual specificity of the Wnt signaling, the experimental systems and designs used in different studies probably influence the cellular responses.
Miyoshi
Keiko
K
Department of Biochemistry, School of Dentistry, The University of Tokushima, Japan.
Hennighausen
Lothar
L
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000235:genetics; D051379:Mice; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin