FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2009285670> ?p ?o ?g. }

• W2009285670 endingPage "3240" @default.
• W2009285670 startingPage "3230" @default.
• W2009285670 abstract "Abstract Purpose: Activating mutations in the BRAF oncogene are found in 8% to 15% of colorectal cancer patients and have been associated with poor survival. In contrast with BRAF-mutant (MT) melanoma, inhibition of the MAPK pathway is ineffective in the majority of BRAFMT colorectal cancer patients. Therefore, identification of novel therapies for BRAFMT colorectal cancer is urgently needed. Experimental Design: BRAFMT and wild-type (WT) colorectal cancer models were assessed in vitro and in vivo. Small-molecule inhibitors of MEK1/2, MET, and HDAC were used, overexpression and siRNA approaches were applied, and cell death was assessed by flow cytometry, Western blotting, cell viability, and caspase activity assays. Results: Increased c-MET-STAT3 signaling was identified as a novel adaptive resistance mechanism to MEK inhibitors (MEKi) in BRAFMT colorectal cancer models in vitro and in vivo. Moreover, MEKi treatment resulted in acute increases in transcription of the endogenous caspase-8 inhibitor c-FLIPL in BRAFMT cells, but not in BRAFWT cells, and inhibition of STAT3 activity abrogated MEKi-induced c-FLIPL expression. In addition, treatment with c-FLIP–specific siRNA or HDAC inhibitors abrogated MEKi-induced upregulation of c-FLIPL expression and resulted in significant increases in MEKi-induced cell death in BRAFMT colorectal cancer cells. Notably, combined HDAC inhibitor/MEKi treatment resulted in dramatically attenuated tumor growth in BRAFMT xenografts. Conclusions: Our findings indicate that c-MET/STAT3-dependent upregulation of c-FLIPL expression is an important escape mechanism following MEKi treatment in BRAFMT colorectal cancer. Thus, combinations of MEKi with inhibitors of c-MET or c-FLIP (e.g., HDAC inhibitors) could be potential novel treatment strategies for BRAFMT colorectal cancer. Clin Cancer Res; 21(14); 3230–40. ©2015 AACR." @default.
• W2009285670 created "2016-06-24" @default.
• W2009285670 creator A5002719979 @default.
• W2009285670 creator A5016266460 @default.
• W2009285670 creator A5017072034 @default.
• W2009285670 creator A5017147519 @default.
• W2009285670 creator A5023638547 @default.
• W2009285670 creator A5054391819 @default.
• W2009285670 creator A5058174847 @default.
• W2009285670 creator A5078841356 @default.
• W2009285670 creator A5081894565 @default.
• W2009285670 creator A5087337816 @default.
• W2009285670 date "2015-07-14" @default.
• W2009285670 modified "2023-10-12" @default.
• W2009285670 title "HDAC Inhibition Overcomes Acute Resistance to MEK Inhibition in <i>BRAF</i>-Mutant Colorectal Cancer by Downregulation of c-FLIPL" @default.
• W2009285670 cites W1597604324 @default.
• W2009285670 cites W1888056807 @default.
• W2009285670 cites W1970766774 @default.
• W2009285670 cites W1988568845 @default.
• W2009285670 cites W1995981641 @default.
• W2009285670 cites W2000581759 @default.
• W2009285670 cites W2014881369 @default.
• W2009285670 cites W2017715430 @default.
• W2009285670 cites W2021920896 @default.
• W2009285670 cites W2027565221 @default.
• W2009285670 cites W2030814605 @default.
• W2009285670 cites W2036045525 @default.
• W2009285670 cites W2042619042 @default.
• W2009285670 cites W2053563072 @default.
• W2009285670 cites W2055624262 @default.
• W2009285670 cites W2057940570 @default.
• W2009285670 cites W2063251760 @default.
• W2009285670 cites W2064862565 @default.
• W2009285670 cites W2089758057 @default.
• W2009285670 cites W2096024381 @default.
• W2009285670 cites W2096283457 @default.
• W2009285670 cites W2102365935 @default.
• W2009285670 cites W2106512898 @default.
• W2009285670 cites W2106543129 @default.
• W2009285670 cites W2110682589 @default.
• W2009285670 cites W2117525838 @default.
• W2009285670 cites W2120164335 @default.
• W2009285670 cites W2120683603 @default.
• W2009285670 cites W2123326378 @default.
• W2009285670 cites W2124662474 @default.
• W2009285670 cites W2128387672 @default.
• W2009285670 cites W2131413118 @default.
• W2009285670 cites W2134142320 @default.
• W2009285670 cites W2134519717 @default.
• W2009285670 cites W2135800465 @default.
• W2009285670 cites W2136474966 @default.
• W2009285670 cites W2141172646 @default.
• W2009285670 cites W2141787711 @default.
• W2009285670 cites W2145070131 @default.
• W2009285670 cites W2148244207 @default.
• W2009285670 cites W2149528253 @default.
• W2009285670 cites W2152490158 @default.
• W2009285670 cites W2156078931 @default.
• W2009285670 cites W2163188200 @default.
• W2009285670 cites W2298065098 @default.
• W2009285670 cites W2326092239 @default.
• W2009285670 cites W2602430582 @default.
• W2009285670 cites W4210372230 @default.
• W2009285670 cites W4246727707 @default.
• W2009285670 doi "https://doi.org/10.1158/1078-0432.ccr-14-2701" @default.
• W2009285670 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4504978" @default.
• W2009285670 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25813020" @default.
• W2009285670 hasPublicationYear "2015" @default.
• W2009285670 type Work @default.
• W2009285670 sameAs 2009285670 @default.
• W2009285670 citedByCount "52" @default.
• W2009285670 countsByYear W20092856702015 @default.
• W2009285670 countsByYear W20092856702016 @default.
• W2009285670 countsByYear W20092856702017 @default.
• W2009285670 countsByYear W20092856702018 @default.
• W2009285670 countsByYear W20092856702019 @default.
• W2009285670 countsByYear W20092856702020 @default.
• W2009285670 countsByYear W20092856702021 @default.
• W2009285670 countsByYear W20092856702022 @default.
• W2009285670 countsByYear W20092856702023 @default.
• W2009285670 crossrefType "journal-article" @default.
• W2009285670 hasAuthorship W2009285670A5002719979 @default.
• W2009285670 hasAuthorship W2009285670A5016266460 @default.
• W2009285670 hasAuthorship W2009285670A5017072034 @default.
• W2009285670 hasAuthorship W2009285670A5017147519 @default.
• W2009285670 hasAuthorship W2009285670A5023638547 @default.
• W2009285670 hasAuthorship W2009285670A5054391819 @default.
• W2009285670 hasAuthorship W2009285670A5058174847 @default.
• W2009285670 hasAuthorship W2009285670A5078841356 @default.
• W2009285670 hasAuthorship W2009285670A5081894565 @default.
• W2009285670 hasAuthorship W2009285670A5087337816 @default.
• W2009285670 hasBestOaLocation W20092856701 @default.
• W2009285670 hasConcept C104317684 @default.
• W2009285670 hasConcept C121608353 @default.
• W2009285670 hasConcept C126322002 @default.
• W2009285670 hasConcept C127561419 @default.
• W2009285670 hasConcept C150903083 @default.
• W2009285670 hasConcept C190283241 @default.

• next