Matches in SemOpenAlex for { <https://semopenalex.org/work/W2119397497> ?p ?o ?g. }
- W2119397497 endingPage "1433" @default.
- W2119397497 startingPage "1427" @default.
- W2119397497 abstract "The tumor suppressor programmed cell death 4 (Pdcd4) is lost in various tumor tissues. Loss of Pdcd4 has been associated with increased tumorigenic potential and tumor progression. While various mechanisms of Pdcd4 regulation have been described, the effect of an inflammatory tumor microenvironment on Pdcd4 protein expression has not been characterized so far. In the present study, we aimed to elucidate the molecular mechanisms of Pdcd4 protein regulation in tumor cells under inflammatory conditions. 12-O-tetradecanoylphorbol 13-acetate-induced differentiation of human U937 monocytes increased the expression and secretion of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-6 and IL-8. Exposure to conditioned medium (CM) of these activated macrophages markedly decreased Pdcd4 protein expression in various tumor cells. Similarly, indirect coculture with such activated U937 monocyte-derived macrophages resulted in the loss of Pdcd4 protein in tumor cells. Decreased Pdcd4 protein levels were attributable to enhanced proteasomal degradation, diminishing Pdcd4 protein half-life. Proteasomal degradation required activation of phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling. Since macrophage-CM sufficed to induce Pdcd4 degradation, Pdcd4 downregulation was determined to be an indirect unidirectional effect of the macrophages on the tumor cells. Pdcd4 protein expression was also attenuated in vivo in mouse colon tissue in response to dextran sodium sulfate-induced colitis. In summary, we characterized PI3K-mTOR-dependent proteasome-mediated Pdcd4 degradation in tumor cells in the inflammatory tumor microenvironment. Consequently, stabilization of Pdcd4 protein could provide a promising novel avenue for therapeutics targeting inflammation-associated tumors." @default.
- W2119397497 created "2016-06-24" @default.
- W2119397497 creator A5017943869 @default.
- W2119397497 creator A5032227105 @default.
- W2119397497 creator A5039208991 @default.
- W2119397497 creator A5048962207 @default.
- W2119397497 creator A5051942824 @default.
- W2119397497 creator A5052677703 @default.
- W2119397497 creator A5056936426 @default.
- W2119397497 creator A5059291199 @default.
- W2119397497 creator A5066201997 @default.
- W2119397497 creator A5079069287 @default.
- W2119397497 creator A5086646466 @default.
- W2119397497 date "2011-07-18" @default.
- W2119397497 modified "2023-10-07" @default.
- W2119397497 title "Inflammation-induced loss of Pdcd4 is mediated by phosphorylation-dependent degradation" @default.
- W2119397497 cites W186292059 @default.
- W2119397497 cites W1970111367 @default.
- W2119397497 cites W1977156161 @default.
- W2119397497 cites W1990561843 @default.
- W2119397497 cites W2011877672 @default.
- W2119397497 cites W2027696262 @default.
- W2119397497 cites W2029845970 @default.
- W2119397497 cites W2038623184 @default.
- W2119397497 cites W2040001751 @default.
- W2119397497 cites W2047790795 @default.
- W2119397497 cites W2050079849 @default.
- W2119397497 cites W2065465954 @default.
- W2119397497 cites W2069104846 @default.
- W2119397497 cites W2075258024 @default.
- W2119397497 cites W2076743940 @default.
- W2119397497 cites W2082046910 @default.
- W2119397497 cites W2102077161 @default.
- W2119397497 cites W2102144390 @default.
- W2119397497 cites W2104052951 @default.
- W2119397497 cites W2111783957 @default.
- W2119397497 cites W2115619054 @default.
- W2119397497 cites W2117692326 @default.
- W2119397497 cites W2123105952 @default.
- W2119397497 cites W2125945390 @default.
- W2119397497 cites W2131687108 @default.
- W2119397497 cites W2131941047 @default.
- W2119397497 cites W2134316882 @default.
- W2119397497 cites W2136166312 @default.
- W2119397497 cites W2141487097 @default.
- W2119397497 cites W2147380958 @default.
- W2119397497 cites W2150633526 @default.
- W2119397497 cites W2151886488 @default.
- W2119397497 cites W2155207590 @default.
- W2119397497 cites W2155639426 @default.
- W2119397497 cites W2159223313 @default.
- W2119397497 cites W2159430811 @default.
- W2119397497 cites W2161011316 @default.
- W2119397497 cites W2162218188 @default.
- W2119397497 cites W2168476365 @default.
- W2119397497 cites W2313630375 @default.
- W2119397497 doi "https://doi.org/10.1093/carcin/bgr131" @default.
- W2119397497 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3179419" @default.
- W2119397497 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21771721" @default.
- W2119397497 hasPublicationYear "2011" @default.
- W2119397497 type Work @default.
- W2119397497 sameAs 2119397497 @default.
- W2119397497 citedByCount "37" @default.
- W2119397497 countsByYear W21193974972012 @default.
- W2119397497 countsByYear W21193974972013 @default.
- W2119397497 countsByYear W21193974972014 @default.
- W2119397497 countsByYear W21193974972015 @default.
- W2119397497 countsByYear W21193974972016 @default.
- W2119397497 countsByYear W21193974972017 @default.
- W2119397497 countsByYear W21193974972018 @default.
- W2119397497 countsByYear W21193974972019 @default.
- W2119397497 countsByYear W21193974972020 @default.
- W2119397497 countsByYear W21193974972021 @default.
- W2119397497 countsByYear W21193974972022 @default.
- W2119397497 countsByYear W21193974972023 @default.
- W2119397497 crossrefType "journal-article" @default.
- W2119397497 hasAuthorship W2119397497A5017943869 @default.
- W2119397497 hasAuthorship W2119397497A5032227105 @default.
- W2119397497 hasAuthorship W2119397497A5039208991 @default.
- W2119397497 hasAuthorship W2119397497A5048962207 @default.
- W2119397497 hasAuthorship W2119397497A5051942824 @default.
- W2119397497 hasAuthorship W2119397497A5052677703 @default.
- W2119397497 hasAuthorship W2119397497A5056936426 @default.
- W2119397497 hasAuthorship W2119397497A5059291199 @default.
- W2119397497 hasAuthorship W2119397497A5066201997 @default.
- W2119397497 hasAuthorship W2119397497A5079069287 @default.
- W2119397497 hasAuthorship W2119397497A5086646466 @default.
- W2119397497 hasBestOaLocation W21193974971 @default.
- W2119397497 hasConcept C104317684 @default.
- W2119397497 hasConcept C127561419 @default.
- W2119397497 hasConcept C164027704 @default.
- W2119397497 hasConcept C17991360 @default.
- W2119397497 hasConcept C185592680 @default.
- W2119397497 hasConcept C190283241 @default.
- W2119397497 hasConcept C203014093 @default.
- W2119397497 hasConcept C2776107976 @default.
- W2119397497 hasConcept C2776914184 @default.
- W2119397497 hasConcept C2781184567 @default.