A new pathway controlling cancer-related inflammation

We have discovered that inactivation of the MAPK ERK5 in epidermal keratinocytes prevented inflammation-driven tumourigenesis in a skin cancer mouse model. Furthermore, suppressing cancer-related inflammation via anti-ERK5 therapy regressed existing tumours and this effect was potentiated by the concurrent administration of sub-therapeutic doses of the chemotherapeutic agent, doxorubicin. These findings have led us to propose that ERK5 is part of a core signal transduction pathway required for inflammation-driven tumourigenesis. Based on this hypothesis, the overall objective of this project is to fully delineate the role of ERK5 signalling in cancer-related inflammation, thereby revealing new avenues for therapeutic cancer research. More specifically, this study will have two aims: first, to identify the molecular basis underlying the inflammatory function of ERK5 in keratinocytes; second, to determine whether constitutive activation of ERK5 in the skin is sufficient to trigger an inflammatory reaction, and as such, constitutes a risk factor for cancer. Overall, this study is highly relevant to human cancer considering that an inflammatory environment is an essential component of all tumours and elevated MEK5/ERK5 expression in human tumours correlates with unfavourable prognosis, shorter disease-free intervals, increased risk of metastasis, and resistance to chemotherapy.