ERK5 is a critical mediator of inflammation-driven cancer

Katherine G Finegan, Diana Perez-Madrigal, James R Hitchin, Clare C Davies, Allan M Jordan, Cathy Tournier

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)742-53
Number of pages12
JournalCancer Research
Volume75
Issue number4
Early online date3 Feb 2015
DOIs
Publication statusPublished - 15 Feb 2015

Keywords

  • Animals
  • Carcinogenesis
  • Carcinogens
  • Epidermis
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inflammation
  • Keratinocytes
  • Mice
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 7
  • Skin Neoplasms

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