The tumor microenvironment supplies pro-inflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL-4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL-4 signaling with the IL-4Rα antagonist IL-4DM compromised breast cancer cell proliferation, invasion and tumor growth by downregulating MAPK pathway activity. IL-4DM reduced numbers of CD44+/CD24- cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-kB. Enforced expression of DUSP4 drove conversion of metastatic cells to non-metastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like properties and spawned metastastic capacity. Targeting IL-4 signaling sensitized breast cancer cells to anti-cancer therapy and strengthened immune responses by enhancing the number of IFN-γ-positive cytotoxic T lymphocytes. Our results showed the role of IL-4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies.
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Publication date: March 2017 Source: Free Radical Biology and Medicine, Volume 104 from #AlexandrosSfakianakis via Alexandros G.Sfak...
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Dtsch med Wochenschr DOI: 10.1055/s-0043-100054 Hintergrund und Fragestellung Ein etablierter Weg, die optimale Behandlung von Tumorpatien...
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Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
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Deepak Thapa, Vanita Ahuja, Deepanshu Dhiman Indian Journal of Anaesthesia 2017 61(12):1012-1014 from #AlexandrosSfakianakis via Alexa...
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Abstract Limited memory size is considered as a major bottleneck in data centers for intelligent urban computing. It is shown that there e...
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ecancer is supporting #BowelCancerAwarenessMonth https://t.co/opXxCAAxzE from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inore...
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Linked Article: Maintz et al. Br J Dermatol 2017; 176:481–487 . from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader h...
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Angelina Jolie’s openness about her diagnosis has undoubtedly raised public awareness of the importance of inherited cancers. Although Desai...
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