TY - JOUR TI - ERK3/MAPK6 controls IL-8 production and chemotaxis AU - Bogucka, Katarzyna AU - Pompaiah, Malvika AU - Marini, Federico AU - Binder, Harald AU - Harms, Gregory AU - Kaulich, Manuel AU - Klein, Matthias AU - Michel, Christian AU - Radsak, Markus P AU - Rosigkeit, Sebastian AU - Grimminger, Peter AU - Schild, Hansjörg AU - Rajalingam, Krishnaraj A2 - Pfeffer, Suzanne R A2 - Ma, Yuting VL - 9 PY - 2020 DA - 2020/04/21 SP - e52511 C1 - eLife 2020;9:e52511 DO - 10.7554/eLife.52511 UR - https://doi.org/10.7554/eLife.52511 AB - ERK3 is a ubiquitously expressed member of the atypical mitogen activated protein kinases (MAPKs) and the physiological significance of its short half-life remains unclear. By employing gastrointestinal 3D organoids, we detect that ERK3 protein levels steadily decrease during epithelial differentiation. ERK3 is not required for 3D growth of human gastric epithelium. However, ERK3 is stabilized and activated in tumorigenic cells, but deteriorates over time in primary cells in response to lipopolysaccharide (LPS). ERK3 is necessary for production of several cellular factors including interleukin-8 (IL-8), in both, normal and tumorigenic cells. Particularly, ERK3 is critical for AP-1 signaling through its interaction and regulation of c-Jun protein. The secretome of ERK3-deficient cells is defective in chemotaxis of neutrophils and monocytes both in vitro and in vivo. Further, knockdown of ERK3 reduces metastatic potential of invasive breast cancer cells. We unveil an ERK3-mediated regulation of IL-8 and epithelial secretome for chemotaxis. KW - MAPK KW - ERK3 KW - secretome KW - metastasis KW - signal transduction KW - chemotaxis KW - IL-8 KW - gastrointestinal organoids JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -