ELIZA

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288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [no cache] 500 found

363) We identified CUX1 as an important modulator of the TAMs phenotype and function by modulating NF-κB-dependent cytokines.

--- 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.

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(1)94 of	(10)7 with	(19)3 for	(28)2 leading
(2)74 null	(11)5 during	(20)3 has	(29)2 mutations
(3)53 and	(12)5 tests	(21)3 over	(30)2 on
(4)47 in	(13)5 that	(22)3 relationships	(31)2 or
(5)17 was	(14)4 among	(23)2 at	(32)2 physical
(6)12 as	(15)4 to	(24)2 but	(33)2 relationship
(7)12 is	(16)4 which	(25)2 can	(34)2 remains
(8)7 Index	(17)3 after	(26)2 could	(35)2 using
(9)7 were	(18)3 by	(27)2 grades

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--- WordNet output for function --- =>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式 Overview of noun function The noun function has 7 senses (first 3 from tagged texts) 1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a mathematical relation such that each element of a given set (the domain of the function) is associated with an element of another set (the range of the function)) 2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 3. (7) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 4. function -- (a relation such that one thing is dependent on another; "height is a function of age"; "price is a function of supply and demand") 5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function") 6. affair, occasion, social occasion, function, social function -- (a vaguely specified social event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly endless round of social functions") 7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger computer program) Overview of verb function The verb function has 3 senses (first 3 from tagged texts) 1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work anymore") 2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table"; "The female students served as a control group"; "This table would serve very well"; "His freedom served him well"; "The table functions as a desk") 3. (1) officiate, function -- (perform duties attached to a particular office or place or function; "His wife officiated as his private secretary") --- WordNet end ---