Matches in SemOpenAlex for { <https://semopenalex.org/work/W2138702921> ?p ?o ?g. }
- W2138702921 endingPage "3668" @default.
- W2138702921 startingPage "3658" @default.
- W2138702921 abstract "Abstract AZD6244 is a small molecule inhibitor of the MEK (MAP/ERK kinase) pathway currently in clinical trials. However, the mechanisms mediating intrinsic resistance to MEK inhibition are not fully characterized. To define molecular mechanisms of MEK inhibitor resistance, we analyzed responses of 38 lung cancer cell lines following AZD6244 treatment and their genome-wide gene expression profiles and identified a panel of genes correlated with sensitivity or resistance to AZD6244 treatment. In particular, ingenuity pathway analysis revealed that activation of the STAT3 pathway was associated with MEK inhibitor resistance. Inhibition of this pathway by JSI-124, a STAT3-specific small molecule inhibitor, or with STAT3-specific siRNA sensitized lung cancer cells to AZD6244 and induced apoptosis. Moreover, combining a STAT3 inhibitor with AZD6244 induced expression of BIM and PARP cleavage, whereas activation of the STAT3 pathway inhibited BIM expression and elicited resistance to MEK inhibitors. We found that the STAT3-regulated microRNA miR-17 played a critical role in MEK inhibitor resistance, such that miR-17 inhibition sensitized resistant cells to AZD6244 by inducing BIM and PARP cleavage. Together, these results indicated that STAT3-mediated overexpression of miR-17 blocked BIM expression and caused resistance to AZD6244. Our findings suggest novel approaches to overcome resistance to MEK inhibitors by combining AZD6244 with STAT3 or miR-17 inhibitors. Cancer Res; 71(10); 3658–68. ©2011 AACR." @default.
- W2138702921 created "2016-06-24" @default.
- W2138702921 creator A5006868141 @default.
- W2138702921 creator A5010128828 @default.
- W2138702921 creator A5023932021 @default.
- W2138702921 creator A5027152610 @default.
- W2138702921 creator A5034128046 @default.
- W2138702921 creator A5035770490 @default.
- W2138702921 creator A5048865240 @default.
- W2138702921 creator A5062277357 @default.
- W2138702921 creator A5073199916 @default.
- W2138702921 date "2011-05-15" @default.
- W2138702921 modified "2023-10-17" @default.
- W2138702921 title "STAT3 Mediates Resistance to MEK Inhibitor through MicroRNA miR-17" @default.
- W2138702921 cites W1789124686 @default.
- W2138702921 cites W1965414206 @default.
- W2138702921 cites W1966464754 @default.
- W2138702921 cites W1967913221 @default.
- W2138702921 cites W1969003435 @default.
- W2138702921 cites W1974091059 @default.
- W2138702921 cites W1977532256 @default.
- W2138702921 cites W1979274840 @default.
- W2138702921 cites W1987359254 @default.
- W2138702921 cites W2001999652 @default.
- W2138702921 cites W2002800994 @default.
- W2138702921 cites W2007847006 @default.
- W2138702921 cites W2009642188 @default.
- W2138702921 cites W2023121881 @default.
- W2138702921 cites W2036534625 @default.
- W2138702921 cites W2038683568 @default.
- W2138702921 cites W2044227662 @default.
- W2138702921 cites W2053439872 @default.
- W2138702921 cites W2058896449 @default.
- W2138702921 cites W2080390713 @default.
- W2138702921 cites W2080686146 @default.
- W2138702921 cites W2085592081 @default.
- W2138702921 cites W2091567220 @default.
- W2138702921 cites W2108274875 @default.
- W2138702921 cites W2114621192 @default.
- W2138702921 cites W2116787167 @default.
- W2138702921 cites W2120434825 @default.
- W2138702921 cites W2120492882 @default.
- W2138702921 cites W2123611729 @default.
- W2138702921 cites W2128445526 @default.
- W2138702921 cites W2129400742 @default.
- W2138702921 cites W2129429534 @default.
- W2138702921 cites W2134829792 @default.
- W2138702921 cites W2137035181 @default.
- W2138702921 cites W2141016223 @default.
- W2138702921 cites W2143838754 @default.
- W2138702921 cites W2145482514 @default.
- W2138702921 cites W2145720555 @default.
- W2138702921 cites W2145988292 @default.
- W2138702921 cites W2148842836 @default.
- W2138702921 cites W2157633567 @default.
- W2138702921 cites W2160770127 @default.
- W2138702921 cites W2167334545 @default.
- W2138702921 doi "https://doi.org/10.1158/0008-5472.can-10-3647" @default.
- W2138702921 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3392199" @default.
- W2138702921 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21444672" @default.
- W2138702921 hasPublicationYear "2011" @default.
- W2138702921 type Work @default.
- W2138702921 sameAs 2138702921 @default.
- W2138702921 citedByCount "85" @default.
- W2138702921 countsByYear W21387029212012 @default.
- W2138702921 countsByYear W21387029212013 @default.
- W2138702921 countsByYear W21387029212014 @default.
- W2138702921 countsByYear W21387029212015 @default.
- W2138702921 countsByYear W21387029212016 @default.
- W2138702921 countsByYear W21387029212017 @default.
- W2138702921 countsByYear W21387029212018 @default.
- W2138702921 countsByYear W21387029212019 @default.
- W2138702921 countsByYear W21387029212020 @default.
- W2138702921 countsByYear W21387029212021 @default.
- W2138702921 countsByYear W21387029212022 @default.
- W2138702921 countsByYear W21387029212023 @default.
- W2138702921 crossrefType "journal-article" @default.
- W2138702921 hasAuthorship W2138702921A5006868141 @default.
- W2138702921 hasAuthorship W2138702921A5010128828 @default.
- W2138702921 hasAuthorship W2138702921A5023932021 @default.
- W2138702921 hasAuthorship W2138702921A5027152610 @default.
- W2138702921 hasAuthorship W2138702921A5034128046 @default.
- W2138702921 hasAuthorship W2138702921A5035770490 @default.
- W2138702921 hasAuthorship W2138702921A5048865240 @default.
- W2138702921 hasAuthorship W2138702921A5062277357 @default.
- W2138702921 hasAuthorship W2138702921A5073199916 @default.
- W2138702921 hasBestOaLocation W21387029211 @default.
- W2138702921 hasConcept C184235292 @default.
- W2138702921 hasConcept C185592680 @default.
- W2138702921 hasConcept C190283241 @default.
- W2138702921 hasConcept C2778923194 @default.
- W2138702921 hasConcept C2781249067 @default.
- W2138702921 hasConcept C502942594 @default.
- W2138702921 hasConcept C54355233 @default.
- W2138702921 hasConcept C57074206 @default.
- W2138702921 hasConcept C62478195 @default.
- W2138702921 hasConcept C86803240 @default.
- W2138702921 hasConcept C95444343 @default.