RNF mutants show enhanced WNT signaling and proliferation

Stable Identifier
R-HSA-5340588
Type
Pathway
Species
Homo sapiens
Compartment
plasma membrane
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RNF mutants show enhanced WNT signaling and proliferation
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RNF43 and related protein ZNRF3 are E3 ubiquitin ligases that negatively regulate WNT signaling by downregulating FZD receptors at the cell surface (Mukai et al, 2010; Hao et al, 2012). Frameshift loss-of-function mutations in RNF43 that enhance WNT signaling have been identified in pancreatic and colorectal cancers; the proliferation of these cells is dependent on the presence of secreted WNT, as their growth is abrogated by treatment of cells with the Porcupine inhibitor LGK974 (Koo et al, 2012; Jiang et al, 2013).

Literature References
PubMed ID Title Journal Year
22575959 ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner

Hao, HX, Xie, Y, Zhang, Y, Charlat, O, Oster, E, Avello, M, Lei, H, Mickanin, C, Liu, D, Ruffner, H, Mao, X, Ma, Q, Zamponi, R, Bouwmeester, T, Finan, PM, Kirschner, MW, Porter, JA, Serluca, FC, Cong, F

Nature 2012
22895187 Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

Koo, BK, Spit, M, Jordens, I, Low, TY, Stange, DE, van De Wetering, M, van Es, JH, Mohammed, S, Heck, AJ, Maurice, MM, Clevers, HC

Nature 2012
20495530 Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt

Mukai, A, Yamamoto-Hino, M, Awano, W, Watanabe, W, Komada, M, Goto, S

EMBO J. 2010
23847203 Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma

Jiang, X, Hao, HX, Growney, JD, Woolfenden, S, Bottiglio, C, Ng, N, Lu, B, Hsieh, MH, Bagdasarian, L, Meyer, R, Smith, TR, Avello, M, Charlat, O, Xie, Y, Porter, JA, Pan, S, Liu, J, McLaughlin, ME, Cong, F

Proc. Natl. Acad. Sci. U.S.A. 2013
Participants
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Participant Of
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Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2014-03-11)
Reviewed
Salahshor, S  (2014-05-12)
Woodgett, J  (2014-05-22)
Created
Rothfels, K  (2014-03-20)