mercredi 3 octobre 2012

Mutated genes in cancer (80) – CTNNB1


In databases :

Ensembl ( ENSG00000168036
UniProt ( P35222
GeneCards ( CTNNB1
HGNC ( 2514 or CTNNB1

Gene locus:


Protein name:

Catenin (cadherin-associated protein), beta 1, 88kDa

Protein size:

781 amino acids; about 88 kDa


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 ubiquitin-proteasome system.

Cancer-related alterations:

Mutations in 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 Jul;17(1):9-26.

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.

Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. Li J, Zhou BP. BMC Cancer. 2011 Feb 1;11:49.

Subtypes of medulloblastoma have distinct developmental origins. Gibson P, Tong Y, Robinson G, Thompson MC, Currle DS, Eden C, Kranenburg TA, Hogg T, Poppleton H, Martin J, Finkelstein D, Pounds S, Weiss A, Patay Z, Scoggins M, Ogg R, Pei Y, Yang ZJ, Brun S, Lee Y, Zindy F, Lindsey JC, Taketo MM, Boop FA, Sanford RA, Gajjar A, Clifford SC, Roussel MF, McKinnon PJ, Gutmann DH, Ellison DW, Wechsler-Reya R, Gilbertson RJ. Nature. 2010 Dec 23;468(7327):1095-9.

Targeting the oncogenic protein beta-catenin to enhance chemotherapy outcome against solid human cancers. Saifo MS, Rempinski DR Jr, Rustum YM, Azrak RG. Mol Cancer. 2010 Dec 2;9:310.

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