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- W2071904977 endingPage "2890" @default.
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- W2071904977 abstract "About half of all melanomas harbor a mutation that results in a constitutively active BRAF kinase mutant (BRAF(V600E/K)) that can be selectively inhibited by targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. Here, we observed marked elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAFi challenge, and decreased the activity of prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth, sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance." @default.
- W2071904977 created "2016-06-24" @default.
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- W2071904977 date "2014-05-27" @default.
- W2071904977 modified "2023-10-16" @default.
- W2071904977 title "WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors" @default.
- W2071904977 cites W1520580849 @default.
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- W2071904977 cites W1651215666 @default.
- W2071904977 cites W1763281581 @default.
- W2071904977 cites W1964026954 @default.
- W2071904977 cites W1965252168 @default.
- W2071904977 cites W1970671407 @default.
- W2071904977 cites W1971947883 @default.
- W2071904977 cites W1972218624 @default.
- W2071904977 cites W1975711182 @default.
- W2071904977 cites W1980906814 @default.
- W2071904977 cites W1982972087 @default.
- W2071904977 cites W1983737852 @default.
- W2071904977 cites W1989121777 @default.
- W2071904977 cites W1994729314 @default.
- W2071904977 cites W1996900960 @default.
- W2071904977 cites W1996965698 @default.
- W2071904977 cites W1999025555 @default.
- W2071904977 cites W2003753849 @default.
- W2071904977 cites W2007867839 @default.
- W2071904977 cites W2017187984 @default.
- W2071904977 cites W2017771787 @default.
- W2071904977 cites W2020543365 @default.
- W2071904977 cites W2020937386 @default.
- W2071904977 cites W2023186669 @default.
- W2071904977 cites W2024085992 @default.
- W2071904977 cites W2025202919 @default.
- W2071904977 cites W2032211985 @default.
- W2071904977 cites W2040467756 @default.
- W2071904977 cites W2043058822 @default.
- W2071904977 cites W2044681816 @default.
- W2071904977 cites W2046585589 @default.
- W2071904977 cites W2055624262 @default.
- W2071904977 cites W2057257265 @default.
- W2071904977 cites W2065914048 @default.
- W2071904977 cites W2069750786 @default.
- W2071904977 cites W2071525523 @default.
- W2071904977 cites W2071742078 @default.
- W2071904977 cites W2075905074 @default.
- W2071904977 cites W2077060638 @default.
- W2071904977 cites W2077893873 @default.
- W2071904977 cites W2078370873 @default.
- W2071904977 cites W2080626878 @default.
- W2071904977 cites W2082027173 @default.
- W2071904977 cites W2099801494 @default.
- W2071904977 cites W2100614336 @default.
- W2071904977 cites W2100887597 @default.
- W2071904977 cites W2102448788 @default.
- W2071904977 cites W2104205745 @default.
- W2071904977 cites W2104866423 @default.
- W2071904977 cites W2104877706 @default.
- W2071904977 cites W2106543129 @default.
- W2071904977 cites W2106606248 @default.
- W2071904977 cites W2110466396 @default.
- W2071904977 cites W2124073148 @default.
- W2071904977 cites W2128542677 @default.
- W2071904977 cites W2139458634 @default.
- W2071904977 cites W2142884277 @default.
- W2071904977 cites W2144096834 @default.
- W2071904977 cites W2145455405 @default.
- W2071904977 cites W2148518190 @default.
- W2071904977 cites W2154196978 @default.
- W2071904977 cites W2156078931 @default.
- W2071904977 cites W2159202112 @default.
- W2071904977 cites W2161018320 @default.
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- W2071904977 doi "https://doi.org/10.1172/jci70156" @default.
- W2071904977 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4071371" @default.
- W2071904977 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24865425" @default.
- W2071904977 hasPublicationYear "2014" @default.
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