FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2183650796> ?p ?o ?g. }

• W2183650796 endingPage "e1913" @default.
• W2183650796 startingPage "e1913" @default.
• W2183650796 abstract "Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with marked chemoresistance and a 5-year survival rate of 7%. The integrated stress response (ISR) is a cytoprotective pathway initiated in response to exposure to various environmental stimuli. We used pancreatic cancer cells (PCCs) that are highly resistant to gemcitabine (Gem) and an orthotopic mouse model to investigate the role of the ISR in Gem chemoresistance. Gem induced eIF2 phosphorylation and downstream transcription factors ATF4 and CHOP in PCCs, and these effects occurred in an eIF2 α -S51 phosphorylation-dependent manner as determined using PANC-1 cells, and wild type and S51 mutant mouse embryo fibroblasts. Blocking the ISR pathway in PCCs with the ISR inhibitor ISRIB or siRNA-mediated depletion of ATF4 resulted in enhanced Gem-mediated apoptosis. Polyribosomal profiling revealed that Gem caused repression of global translation and this effect was reversed by ISRIB or by expressing GADD34 to facilitate eIF2 dephosphorylation. Moreover, Gem promoted preferential mRNA translation as determined in a TK-ATF4 5′UTR-Luciferase reporter assay, and this effect was also reversed by ISRIB. RNA-seq analysis revealed that Gem upregulated eIF2 and Nrf2 pathways, and that ISRIB significantly inhibited these pathways. Gem also induced the expression of the antiapoptotic factors Nupr1, BEX2, and Bcl2a1, whereas ISRIB reduced their expression. In an orthotopic tumor model using PANC-1 cells, ISRIB facilitated Gem-mediated increases in PARP cleavage, which occurred in conjunction with decreased tumor size. These findings indicate that Gem chemoresistance is enhanced by activating multiple ISR-dependent pathways, including eIF2, Nrf2, Nupr1, BEX2, and Bcl2A1. It is suggested that targeting the ISR pathway may be an efficient mechanism for enhancing therapeutic responsiveness to Gem in PDAC." @default.
• W2183650796 created "2016-06-24" @default.
• W2183650796 creator A5001771481 @default.
• W2183650796 creator A5052428479 @default.
• W2183650796 creator A5055597936 @default.
• W2183650796 creator A5080448023 @default.
• W2183650796 creator A5088156146 @default.
• W2183650796 date "2015-10-15" @default.
• W2183650796 modified "2023-10-14" @default.
• W2183650796 title "Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma" @default.
• W2183650796 cites W1968486675 @default.
• W2183650796 cites W1977603207 @default.
• W2183650796 cites W1979342940 @default.
• W2183650796 cites W1980438612 @default.
• W2183650796 cites W1982081954 @default.
• W2183650796 cites W1987313243 @default.
• W2183650796 cites W1991046191 @default.
• W2183650796 cites W1991250346 @default.
• W2183650796 cites W2003924215 @default.
• W2183650796 cites W2015569627 @default.
• W2183650796 cites W2017463076 @default.
• W2183650796 cites W2020189113 @default.
• W2183650796 cites W2021251343 @default.
• W2183650796 cites W2023374667 @default.
• W2183650796 cites W2023571913 @default.
• W2183650796 cites W2027821655 @default.
• W2183650796 cites W2028113479 @default.
• W2183650796 cites W2030630092 @default.
• W2183650796 cites W2044821390 @default.
• W2183650796 cites W2046278771 @default.
• W2183650796 cites W2051615139 @default.
• W2183650796 cites W2057371955 @default.
• W2183650796 cites W2058258296 @default.
• W2183650796 cites W2061594475 @default.
• W2183650796 cites W2067040999 @default.
• W2183650796 cites W2073604155 @default.
• W2183650796 cites W2074471441 @default.
• W2183650796 cites W2075188262 @default.
• W2183650796 cites W2081341738 @default.
• W2183650796 cites W2085487477 @default.
• W2183650796 cites W2086699218 @default.
• W2183650796 cites W2089039955 @default.
• W2183650796 cites W2102690338 @default.
• W2183650796 cites W2109535551 @default.
• W2183650796 cites W2110420807 @default.
• W2183650796 cites W2117692326 @default.
• W2183650796 cites W2118337893 @default.
• W2183650796 cites W2126780194 @default.
• W2183650796 cites W2127848114 @default.
• W2183650796 cites W2128327076 @default.
• W2183650796 cites W2130326770 @default.
• W2183650796 cites W2131632095 @default.
• W2183650796 cites W2138155367 @default.
• W2183650796 cites W2139529165 @default.
• W2183650796 cites W2140343175 @default.
• W2183650796 cites W2145963785 @default.
• W2183650796 cites W2151048225 @default.
• W2183650796 cites W2151253787 @default.
• W2183650796 cites W2152239989 @default.
• W2183650796 cites W2158288339 @default.
• W2183650796 cites W2159104053 @default.
• W2183650796 cites W2161884651 @default.
• W2183650796 cites W2161910662 @default.
• W2183650796 cites W2163832829 @default.
• W2183650796 cites W2165480504 @default.
• W2183650796 cites W2166063624 @default.
• W2183650796 cites W2167277749 @default.
• W2183650796 cites W2169961966 @default.
• W2183650796 cites W2170202192 @default.
• W2183650796 cites W4229719081 @default.
• W2183650796 doi "https://doi.org/10.1038/cddis.2015.264" @default.
• W2183650796 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4632294" @default.
• W2183650796 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26469962" @default.
• W2183650796 hasPublicationYear "2015" @default.
• W2183650796 type Work @default.
• W2183650796 sameAs 2183650796 @default.
• W2183650796 citedByCount "90" @default.
• W2183650796 countsByYear W21836507962016 @default.
• W2183650796 countsByYear W21836507962017 @default.
• W2183650796 countsByYear W21836507962018 @default.
• W2183650796 countsByYear W21836507962019 @default.
• W2183650796 countsByYear W21836507962020 @default.
• W2183650796 countsByYear W21836507962021 @default.
• W2183650796 countsByYear W21836507962022 @default.
• W2183650796 countsByYear W21836507962023 @default.
• W2183650796 crossrefType "journal-article" @default.
• W2183650796 hasAuthorship W2183650796A5001771481 @default.
• W2183650796 hasAuthorship W2183650796A5052428479 @default.
• W2183650796 hasAuthorship W2183650796A5055597936 @default.
• W2183650796 hasAuthorship W2183650796A5080448023 @default.
• W2183650796 hasAuthorship W2183650796A5088156146 @default.
• W2183650796 hasBestOaLocation W21836507961 @default.
• W2183650796 hasConcept C104317684 @default.
• W2183650796 hasConcept C105580179 @default.
• W2183650796 hasConcept C11960822 @default.
• W2183650796 hasConcept C121608353 @default.
• W2183650796 hasConcept C139447449 @default.
• W2183650796 hasConcept C149364088 @default.

• next