ELIZA

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290904 occurrences (No.84 in the rank) during 5 years in the PubMed. [no cache] 500 found

207) We could demonstrate that CUX1 interacts with NF-κB p65, leading to reduced binding of NF-κB p65 to the chemokine promoters.

--- ABSTRACT ---

PMID:24336331 DOI:10.1038/onc.2013.530

2015 Oncogene

* CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling.

- Many solid cancers including pancreatic ductal adenocarcinoma (PDAC) are characterized by an extensive stromal reaction that is accompanied by infiltrating tumor-associated macrophages (TAMs). The role of TAMs in malignant tumors is only partially understood. Previously, we identified the transcription factor CUX1 as an important mediator of tumor progression in PDAC. Interestingly, we found that CUX1 is highly expressed not only in tumor cells but also in TAMs. On the basis of these data, we aimed to elucidate the effects of CUX1 in TAMs in vitro and in vivo. We analyzed the effects of CUX1 on cytokine expression using overexpression and knockdown strategies. The cytokine regulation by CUX1 was further assessed by reporter assays, DNA pulldown experiments and chromatin-immunoprecipitation. CUX1 expression in TAMs was analyzed in human pancreatic cancer tissues and in a genetic mouse model. Immunohistochemical analysis revealed strong expression levels of CUX1 in a distinct subset of TAMs in human PDAC tissues. Furthermore, its expression increased during tumor progression in a genetic mouse model of PDAC. Profiling experiments showed that CUX1 downregulates several NF-κB-regulated chemokines such as CXCL10, which have been associated with M1 polarization and inhibition of angiogenesis and tumor progression. We could demonstrate that CUX1 interacts with NF-κB p65, leading to reduced binding of NF-κB p65 to the chemokine promoters. In addition, CUX1 reduces acetylation of NF-κB p65 at K310 by recruiting HDAC1. Functionally, CUX1 expression in TAMs antagonizes T-cell attraction and enhances angiogenesis in vitro. We identified CUX1 as an important modulator of the TAMs phenotype and function by modulating NF-κB-dependent cytokines.

--- ABSTRACT END ---

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(1)66 the	(12)4 activity	(24)2 among	(35)2 interhemispheric
(2)30 in	(13)4 both	(25)2 availability	(36)2 it
(3)23 by	(14)4 cell	(26)2 blood	(37)2 likelihood
(4)13 null	(16)3 ability	(27)2 but	(38)2 number
(5)13 to	(17)3 after	(28)2 compared	(39)2 rates
(6)10 glutathione	(18)3 binding	(29)2 effortful	(40)2 stem
(7)8 and	(19)3 or	(30)2 ejection	(41)2 total
(8)8 expression	(20)3 risk	(31)2 following	(42)2 tumor
(9)5 levels	(21)3 sensitivity	(32)2 from	(43)2 which
(10)5 significantly	(22)2 (P	(33)2 glutathione,
(11)4 PGE2	(23)2 BRCA-1	(34)2 hippocampal

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--- WordNet output for reduced --- =>貧しい暮らし, 落ちぶれた生活 Overview of verb reduce The verb reduce has 20 senses (first 11 from tagged texts) 1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on; make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health benefits") 2. (9) reduce -- (make less complex; "reduce a problem to a single question") 3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to slavery") 4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one term for another) 5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She reduced her niece to a servant") 6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a compromise") 7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater"; "Can you shrink this image?") 8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living") 9. (1) reduce, scale down -- (make smaller; "reduce an image") 10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with hydrogen or form a hydride, or to undergo an increase in the number of electrons) 11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners") 12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently"; "The rich landowners subjugated the peasants working the land") 13. reduce -- (undergo meiosis; "The cells reduce") 14. reduce -- (reposition (a broken bone after surgery) back to its normal site) 15. reduce -- (destress and thus weaken a sound when pronouncing it) 16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while retaining essential elements; "The manuscript must be shortened") 17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The sauce should reduce to one cup") 18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the sauce by boiling it for a long time") 19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture; "cut bourbon") 20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight) Overview of adj reduced The adj reduced has 2 senses (first 2 from tagged texts) 1. (6) decreased, reduced -- (made less in size or amount or degree) 2. (1) reduced, rock-bottom -- (well below normal (especially in price)) --- WordNet end ---