Signaling by WNT in cancer

Stable Identifier
R-HSA-4791275
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The WNT signaling pathway has been linked with cancer ever since the identification of the first WNT as a gene activated by integration of mouse mammary tumor virus proviral DNA in virally-induced breast tumors (Nusse et al, 1984). The most well known example of aberrant WNT signaling in cancer is in colorectal cancer, where an activating mutation in a WNT pathway component is seen in 90% of sporadic cases. Inappropriate WNT pathway activation has also been implicated in most other solid human cancers but is not always associated with mutations in WNT pathway components (reviewed in Polakis, 2012).
Both tumor suppressors and oncogenes have been identified in the so-called canonical WNT pathway, which regulates WNT-dependent transcription by promoting the degradation of beta-catenin in the absence of ligand (reviewed in Polakis, 2012). Loss-of-function mutations in the destruction complex components APC, Axin and AMER1 and gain-of-function mutations in beta-catenin itself cause constitutive signaling and are found in cancers of the intestine, kidney, liver and stomach, among others (Polakis, 1995; Segiditsas and Tomlinson, 2006; Peifer and Polakis, 2000; Laurent-Puig et al, 2001; Liu et al, 2000; Satoh et al, 2000; Major et al, 2007; Ruteshouser et al, 2008). WNTs and WNT pathway components are also frequently over- or under-expressed in various cancers, and these changes are correlated with epigenetic regulation of promoter activity. In some contexts, both the canonical and non-canonical WNT signaling, which governs processes such as cell polarity and morphogenesis, may also contribute to tumor formation by promoting cell migration, invasiveness and metastasis.

Literature References
PubMed ID Title Journal Year
11375957 Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

Laurent-Puig, P, Legoix, P, Bluteau, O, Belghiti, J, Franco, D, Binot, F, Monges, G, Thomas, G, Bioulac-Sage, P, Zucman-Rossi, J

Gastroenterology 2001
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
22438566 Wnt signaling in cancer

Polakis, P

Cold Spring Harb Perspect Biol 2012
10733430 Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus

Peifer, M, Polakis, P

Science 2000
7749328 Mutations in the APC gene and their implications for protein structure and function

Polakis, P

Curr. Opin. Genet. Dev. 1995
6318122 Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15

Nusse, R, van Ooyen, A, Cox, D, Fung, YK, Varmus, H

Nature 1984
17143297 Colorectal cancer and genetic alterations in the Wnt pathway

Segditsas, S, Tomlinson, I

Oncogene 2006
17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling

Major, MB, Camp, ND, Berndt, JD, Yi, X, Goldenberg, SJ, Hubbert, C, Biechele, TL, Gingras, AC, Zheng, N, Maccoss, MJ, Angers, S, Moon, RT

Science 2007
18311776 Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors

Ruteshouser, EC, Robinson, SM, Huff, V

Genes Chromosomes Cancer 2008
Participants
Participant Of
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed