Matches in SemOpenAlex for { <https://semopenalex.org/work/W4214510985> ?p ?o ?g. }
- W4214510985 abstract "Abstract Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selectively controls their transport and translation during adaptation to BRAF-targeted therapy. UHMK1 inactivation induces cell death by disrupting therapy induced metabolic reprogramming, and importantly, delays resistance to BRAF and MEK combination therapy in multiple in vivo models. We propose selective mRNA processing and translation by UHMK1 constitutes a mechanism of non-genetic resistance to targeted therapy in melanoma by controlling metabolic plasticity induced by therapy." @default.
- W4214510985 created "2022-03-02" @default.
- W4214510985 creator A5000821929 @default.
- W4214510985 creator A5003030781 @default.
- W4214510985 creator A5005394146 @default.
- W4214510985 creator A5009720444 @default.
- W4214510985 creator A5010814224 @default.
- W4214510985 creator A5022922854 @default.
- W4214510985 creator A5027942855 @default.
- W4214510985 creator A5029741499 @default.
- W4214510985 creator A5038686903 @default.
- W4214510985 creator A5041530254 @default.
- W4214510985 creator A5042619999 @default.
- W4214510985 creator A5043756798 @default.
- W4214510985 creator A5043958529 @default.
- W4214510985 creator A5044516621 @default.
- W4214510985 creator A5044726580 @default.
- W4214510985 creator A5045056236 @default.
- W4214510985 creator A5048111860 @default.
- W4214510985 creator A5053459565 @default.
- W4214510985 creator A5053539463 @default.
- W4214510985 creator A5060586557 @default.
- W4214510985 creator A5067671868 @default.
- W4214510985 creator A5075334767 @default.
- W4214510985 creator A5075828517 @default.
- W4214510985 creator A5087924478 @default.
- W4214510985 creator A5090704221 @default.
- W4214510985 date "2022-03-01" @default.
- W4214510985 modified "2023-10-16" @default.
- W4214510985 title "Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma" @default.
- W4214510985 cites W1163924930 @default.
- W4214510985 cites W1528632786 @default.
- W4214510985 cites W1540853973 @default.
- W4214510985 cites W1553978925 @default.
- W4214510985 cites W1640505003 @default.
- W4214510985 cites W1834835434 @default.
- W4214510985 cites W1910950086 @default.
- W4214510985 cites W1958855774 @default.
- W4214510985 cites W1965370740 @default.
- W4214510985 cites W1978874148 @default.
- W4214510985 cites W1979245259 @default.
- W4214510985 cites W2001338718 @default.
- W4214510985 cites W2009897007 @default.
- W4214510985 cites W2031134972 @default.
- W4214510985 cites W2033708806 @default.
- W4214510985 cites W2037513168 @default.
- W4214510985 cites W2041554446 @default.
- W4214510985 cites W2065572350 @default.
- W4214510985 cites W2086638152 @default.
- W4214510985 cites W2087102300 @default.
- W4214510985 cites W2092021778 @default.
- W4214510985 cites W2098273883 @default.
- W4214510985 cites W2104697581 @default.
- W4214510985 cites W2105747169 @default.
- W4214510985 cites W2106391833 @default.
- W4214510985 cites W2121545342 @default.
- W4214510985 cites W2123879591 @default.
- W4214510985 cites W2125143689 @default.
- W4214510985 cites W2133154786 @default.
- W4214510985 cites W2140163306 @default.
- W4214510985 cites W2150099889 @default.
- W4214510985 cites W2154668905 @default.
- W4214510985 cites W2159220884 @default.
- W4214510985 cites W2159707944 @default.
- W4214510985 cites W2167195670 @default.
- W4214510985 cites W2174381910 @default.
- W4214510985 cites W2322378248 @default.
- W4214510985 cites W2577256604 @default.
- W4214510985 cites W2609617692 @default.
- W4214510985 cites W2620403292 @default.
- W4214510985 cites W2729334679 @default.
- W4214510985 cites W2773011778 @default.
- W4214510985 cites W2775647070 @default.
- W4214510985 cites W2777985045 @default.
- W4214510985 cites W2781583063 @default.
- W4214510985 cites W2808878318 @default.
- W4214510985 cites W2884607428 @default.
- W4214510985 cites W2891587993 @default.
- W4214510985 cites W2932166412 @default.
- W4214510985 cites W2975051965 @default.
- W4214510985 cites W2995196829 @default.
- W4214510985 cites W3000780610 @default.
- W4214510985 cites W3029402610 @default.
- W4214510985 cites W3092419705 @default.
- W4214510985 cites W3092607059 @default.
- W4214510985 cites W3093185906 @default.
- W4214510985 cites W3098262867 @default.
- W4214510985 cites W3167360675 @default.
- W4214510985 cites W3177828909 @default.
- W4214510985 doi "https://doi.org/10.1038/s41467-022-28705-x" @default.
- W4214510985 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35232962" @default.
- W4214510985 hasPublicationYear "2022" @default.
- W4214510985 type Work @default.
- W4214510985 citedByCount "7" @default.
- W4214510985 countsByYear W42145109852021 @default.
- W4214510985 countsByYear W42145109852022 @default.
- W4214510985 countsByYear W42145109852023 @default.
- W4214510985 crossrefType "journal-article" @default.
- W4214510985 hasAuthorship W4214510985A5000821929 @default.
- W4214510985 hasAuthorship W4214510985A5003030781 @default.