AXIN mutants destabilize the destruction complex, activating WNT signaling

Stable Identifier
R-HSA-4839735
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Pathway
Species
Homo sapiens
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AXIN1 and AXIN2 are critical scaffolding proteins of the beta-catenin destruction complex and make protein-protein interactions with several of the other complex components including APC, GSK3, CK1 and beta-catenin itself through specific domains (reviewed in Saito-Diaz et al, 2013). Because of its role in promoting the degradation of beta-catenin and thereby restricting WNT signaling, AXIN1 is regarded as a tumor suppressor; consistent with this, biallelic mutations in AXIN1 that abrogate its expression or result in the production of truncated proteins have been identified in some human cancers, notably in hepatocellular and colorectal carcinomas and medullobalstoma (Satoh et al, 2000; Taniguchi et al, 2002; Shimizu et al, 2002; Dahmen et al, 2001; reviewed in Salahshor and Woodgett, 2005).

Literature References
PubMed ID Title Journal Year
10700176 AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1

Satoh, S, Daigo, Y, Furukawa, Y, Kato, T, Miwa, N, Nishiwaki, T, Kawasoe, T, Ishiguro, H, Fujita, M, Tokino, T, Sasaki, Y, Imaoka, S, Murata, M, Shimano, T, Yamaoka, Y, Nakamura, Y

Nat. Genet. 2000
15735151 The links between axin and carcinogenesis

Salahshor, S, Woodgett, JR

J. Clin. Pathol. 2005
11585731 Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas

Dahmen, RP, Koch, A, Denkhaus, D, Tonn, JC, Sörensen, N, Berthold, F, Behrens, J, Birchmeier, W, Wiestler, OD, Pietsch, T

Cancer Res. 2001
23256519 The way Wnt works: Components and mechanism

Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E

Growth Factors 2013
11746989 Frequent alterations in the Wnt signaling pathway in colorectal cancer with microsatellite instability

Shimizu, Y, Ikeda, S, Fujimori, M, Kodama, S, Nakahara, M, Okajima, M, Asahara, T

Genes Chromosomes Cancer 2002
12101426 Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas

Taniguchi, K, Roberts, LR, Aderca, IN, Dong, X, Qian, C, Murphy, LM, Nagorney, DM, Burgart, LJ, Roche, PC, Smith, DI, Ross, JA, Liu, W

Oncogene 2002
Participants
Participant Of
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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Created