title: ERK5 is a critical mediator of inflammation-driven cancer.
abstract: Chronic inflammation is a hallmark of many cancers, yet the pathogenic mechanisms that distinguish cancer-associated inflammation from benign persistent inflammation are still mainly unclear. Here, we report that the protein kinase ERK5 controls the expression of a specific subset of inflammatory mediators in the mouse epidermis, which triggers the recruitment of inflammatory cells needed to support skin carcinogenesis. Accordingly, inactivation of ERK5 in keratinocytes prevents inflammation-driven tumorigenesis in this model. In addition, we found that anti-ERK5 therapy cooperates synergistically with existing antimitotic regimens, enabling efficacy of subtherapeutic doses. Collectively, our findings identified ERK5 as a mediator of cancer-associated inflammation in the setting of epidermal carcinogenesis. Considering that ERK5 is expressed in almost all tumor types, our findings suggest that targeting tumor-associated inflammation via anti-ERK5 therapy may have broad implications for the treatment of human tumors.
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. cathy.tournier@manchester.ac.uk k.g.finegan@manchester.ac.uk.
authors: Katherine G
authors: KG
authors: Finegan
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Diana
authors: D
authors: Perez-Madrigal
authors: Drug Discovery Unit Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
authors: James R
authors: JR
authors: Hitchin
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors: Clare C
authors: CC
authors: Davies
authors: Drug Discovery Unit Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
authors: Allan M
authors: AM
authors: Jordan
authors: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. cathy.tournier@manchester.ac.uk k.g.finegan@manchester.ac.uk.
authors: Cathy
authors: C
authors: Tournier
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D048054:Mitogen-Activated Protein Kinase 7 / Q000096:biosynthesis* / Q000235:genetics; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: D002273:Carcinogens; D048054:Mitogen-Activated Protein Kinase 7
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