RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F21%3A00119379" target="_blank" >RIV/00216224:14310/21:00119379 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/21:00554437 RIV/00159816:_____/21:00075053
Result on the web
<a href="https://elifesciences.org/articles/65759#info" target="_blank" >https://elifesciences.org/articles/65759#info</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.7554/eLife.65759" target="_blank" >10.7554/eLife.65759</a>
Alternative languages
Result language
angličtina
Original language name
RNF43 inhibits WNT5A-driven signaling and suppresses melanoma invasion and resistance to the targeted therapy
Original language description
RNF43 is an E3 ubiquitin ligase and known negative regulator of WNT/beta-catenin signaling. We demonstrate that RNF43 is also a regulator of noncanonical WNT5A-induced signaling in human cells. Analysis of the RNF43 interactome using BioID and immunoprecipitation showed that RNF43 can interact with the core receptor complex components dedicated to the noncanonical Wnt pathway such as ROR1, ROR2, VANGL1, and VANGL2. RNF43 triggers VANGL2 ubiquitination and proteasomal degradation and clathrin-dependent internalization of ROR1 receptor and inhibits ROR2 activation. These activities of RNF43 are physiologically relevant and block pro-metastatic WNT5A signaling in melanoma. RNF43 inhibits responses to WNT5A, which results in the suppression of invasive properties of melanoma cells. Furthermore, RNF43 prevented WNT5A-assisted development of resistance to BRAF V600E and MEK inhibitors. Next, RNF43 acted as melanoma suppressor and improved response to targeted therapies in vivo. In line with these findings, RNF43 expression decreases during melanoma progression and RNF43-low patients have a worse prognosis. We conclude that RNF43 is a newly discovered negative regulator of WNT5A-mediated biological responses that desensitizes cells to WNT5A.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
eLife
ISSN
2050-084X
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
October
Country of publishing house
GB - UNITED KINGDOM
Number of pages
41
Pages from-to
„e65759“
UT code for WoS article
000712036700001
EID of the result in the Scopus database
2-s2.0-85118492946