* 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.
=>確認飛行物体;略:IFO
Overview of verb identify
The verb identify has 6 senses (first 6 from tagged texts)
1. (32) identify, place -- (recognize as being; establish the identity of someone or something; "She
identified the man on the 'wanted' poster")
2. (7) name, identify -- (give the name or identifying characteristics of; refer to by name or some
other identifying characteristic property; "Many senators were named in connection with the
scandal"; "The almanac identifies the auspicious months")
3. (6) identify -- (consider (oneself) as similar to somebody else; "He identified with the
refugees")
4. (4) identify -- (conceive of as united or associated; "Sex activity is closely identified with
the hypothalamus")
5. (2) identify, discover, key, key out, distinguish, describe, name -- (identify as in botany or
biology, for example)
6. (2) identify -- (consider to be equal or the same; "He identified his brother as one of the
fugitives")
Overview of adj identified
The adj identified has 1 sense (first 1 from tagged texts)
1. (1) identified -- (having the identity known or established; "the identified bodies were released
for burial")
--- WordNet end ---