Beta-catenin, the protein encoded by
CTNNB1 has important functions in the E-cadherin-mediated cell-cell adhesion
system and also as a downstream signaling molecule in the Wnt pathway.
Cytoplasmic accumulation of beta-catenin allows it to translocate to the
nucleus to form complexes with transcription factors of the T cell
factor-lymphoid enhancer factor (Tcf-Lef) family. Beta-catenin is assumed to
transactivate mostly unknown target genes, which may stimulate cell
proliferation (acts as an oncogene) or inhibit apoptosis. The beta-catenin
level in the cell is regulated by its association with the adenomatous
polyposis coli (APC) tumor suppressor protein, axin and GSK-3b. Phosphorylation
of beta-catenin by the APC-axin-GSK-3b complex leads to its degradation by the
this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR),
medulloblastoma (MDB), and ovarian cancer. Three transcript variants encoding
the same protein have been found for this gene.
Somatic point mutations have been observed
in various (almost all) types of cancers, with high levels (>20%) in cancers
of soft tissues, pancreas, pituitary, liver, endometrium, adrenal glands,
colon. Beta-catenin alteration may facilitate the development of hepatocellular
carcinoma in the course of chronic hepatitis. Somatic
CTNNB1 mutations have also been found in
ovarian carcinoma, medulloblastoma (a malignant, invasive embryonal tumor of
the cerebellum with a preferential manifestation in children), and pilomatrixoma
(a common benign skin tumor).
Mutations are observed mostly in regions
corresponding to the first 75 amino acids. Substitution hot spots ( “missense”,
in most cases) correspond to amino acids 34, 37, 40, 45.
Of note, a chromosomal aberration
involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most
common benign epithelial tumors of the salivary gland. Translocation
t(3;8)(p21;q12) fuse a portion of CTNNB1 with PLAG1.
References (open access):
Wnt/beta-catenin signaling: components,
mechanisms, and diseases. MacDonald BT, Tamai K, He X. Dev Cell. 2009
Mutated beta-catenin evades a
microRNA-dependent regulatory loop. Veronese A, Visone R, Consiglio J, Acunzo
M, Lupini L, Kim T, Ferracin M, Lovat F, Miotto E, Balatti V, D'Abundo L,
Gramantieri L, Bolondi L, Pekarsky Y, Perrotti D, Negrini M, Croce CM. Proc
Natl Acad Sci U S A. 2011 Mar 22;108(12):4840-5.