Matches in SemOpenAlex for { <https://semopenalex.org/work/W2980083519> ?p ?o ?g. }
- W2980083519 endingPage "2326" @default.
- W2980083519 startingPage "2316" @default.
- W2980083519 abstract "Oncogenic RAS provides crucial survival signaling for up to half of multiple myeloma cases, but has so far remained a clinically undruggable target. RAL is a member of the RAS superfamily of small GTPases and is considered to be a potential mediator of oncogenic RAS signaling. In primary multiple myeloma, we found RAL to be overexpressed in the vast majority of samples when compared with pre-malignant monoclonal gammopathy of undetermined significance or normal plasma cells. We analyzed the functional effects of RAL abrogation in myeloma cell lines and found that RAL is a critical mediator of survival. RNAi-mediated knockdown of RAL resulted in rapid induction of tumor cell death, an effect which was independent from signaling via mitogen-activated protein kinase, but appears to be partially dependent on Akt activity. Notably, RAL activation was not correlated with the presence of activating RAS mutations and remained unaffected by knockdown of oncogenic RAS. Furthermore, transcriptome analysis yielded distinct RNA expression signatures after knockdown of either RAS or RAL. Combining RAL depletion with clinically relevant anti-myeloma agents led to enhanced rates of cell death. Our data demonstrate that RAL promotes multiple myeloma cell survival independently of oncogenic RAS and, thus, this pathway represents a potential therapeutic target in its own right." @default.
- W2980083519 created "2019-10-18" @default.
- W2980083519 creator A5013957088 @default.
- W2980083519 creator A5015286734 @default.
- W2980083519 creator A5016360607 @default.
- W2980083519 creator A5023427775 @default.
- W2980083519 creator A5024436174 @default.
- W2980083519 creator A5028397596 @default.
- W2980083519 creator A5029898558 @default.
- W2980083519 creator A5050331440 @default.
- W2980083519 creator A5057050411 @default.
- W2980083519 creator A5058818082 @default.
- W2980083519 creator A5059065322 @default.
- W2980083519 creator A5065834452 @default.
- W2980083519 creator A5076386757 @default.
- W2980083519 creator A5080827305 @default.
- W2980083519 creator A5084766894 @default.
- W2980083519 creator A5086655742 @default.
- W2980083519 creator A5087780010 @default.
- W2980083519 date "2019-10-10" @default.
- W2980083519 modified "2023-10-16" @default.
- W2980083519 title "RAL GTPases mediate multiple myeloma cell survival and are activated independently of oncogenic RAS" @default.
- W2980083519 cites W1911236670 @default.
- W2980083519 cites W1968036059 @default.
- W2980083519 cites W1977918009 @default.
- W2980083519 cites W1982967858 @default.
- W2980083519 cites W1988878042 @default.
- W2980083519 cites W1988911160 @default.
- W2980083519 cites W1990705108 @default.
- W2980083519 cites W1992880310 @default.
- W2980083519 cites W2001979983 @default.
- W2980083519 cites W2006104341 @default.
- W2980083519 cites W2006603416 @default.
- W2980083519 cites W2008183550 @default.
- W2980083519 cites W2010890298 @default.
- W2980083519 cites W2013036515 @default.
- W2980083519 cites W2015577159 @default.
- W2980083519 cites W2018978055 @default.
- W2980083519 cites W2022920832 @default.
- W2980083519 cites W2031692900 @default.
- W2980083519 cites W2035943570 @default.
- W2980083519 cites W2038783205 @default.
- W2980083519 cites W2050453122 @default.
- W2980083519 cites W2066793047 @default.
- W2980083519 cites W2073245743 @default.
- W2980083519 cites W2076865122 @default.
- W2980083519 cites W2079479702 @default.
- W2980083519 cites W2080752012 @default.
- W2980083519 cites W2081990599 @default.
- W2980083519 cites W2095020121 @default.
- W2980083519 cites W2101035019 @default.
- W2980083519 cites W2123429489 @default.
- W2980083519 cites W2128434997 @default.
- W2980083519 cites W2128826373 @default.
- W2980083519 cites W2129242642 @default.
- W2980083519 cites W2130560835 @default.
- W2980083519 cites W2136940817 @default.
- W2980083519 cites W2165928290 @default.
- W2980083519 cites W2165994717 @default.
- W2980083519 cites W2170776626 @default.
- W2980083519 cites W2214074259 @default.
- W2980083519 cites W2221534131 @default.
- W2980083519 cites W2223921723 @default.
- W2980083519 cites W2289028046 @default.
- W2980083519 cites W2294570978 @default.
- W2980083519 cites W2295798984 @default.
- W2980083519 cites W2296755350 @default.
- W2980083519 cites W2339828620 @default.
- W2980083519 cites W2468731336 @default.
- W2980083519 cites W2492626689 @default.
- W2980083519 cites W2515077761 @default.
- W2980083519 cites W2525590025 @default.
- W2980083519 cites W2612968490 @default.
- W2980083519 cites W2765084883 @default.
- W2980083519 cites W2773731465 @default.
- W2980083519 cites W2782799955 @default.
- W2980083519 cites W2785345346 @default.
- W2980083519 cites W2791471681 @default.
- W2980083519 cites W2808562996 @default.
- W2980083519 cites W2887329673 @default.
- W2980083519 cites W2922297077 @default.
- W2980083519 cites W4250636261 @default.
- W2980083519 doi "https://doi.org/10.3324/haematol.2019.223024" @default.
- W2980083519 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7556628" @default.
- W2980083519 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33054056" @default.
- W2980083519 hasPublicationYear "2019" @default.
- W2980083519 type Work @default.
- W2980083519 sameAs 2980083519 @default.
- W2980083519 citedByCount "12" @default.
- W2980083519 countsByYear W29800835192020 @default.
- W2980083519 countsByYear W29800835192021 @default.
- W2980083519 countsByYear W29800835192022 @default.
- W2980083519 countsByYear W29800835192023 @default.
- W2980083519 crossrefType "journal-article" @default.
- W2980083519 hasAuthorship W2980083519A5013957088 @default.
- W2980083519 hasAuthorship W2980083519A5015286734 @default.
- W2980083519 hasAuthorship W2980083519A5016360607 @default.
- W2980083519 hasAuthorship W2980083519A5023427775 @default.