TBK1, an NF-κB activating kinase, is required for platelet-induced EMT
(English)Manuscript (preprint) (Other academic)
Platelets can promote several steps during the metastatic process, and hence
contribute to malignant progression. During early stages of metastasis, platelets
promote invasive properties of tumor cells by induction of epithelial to mesenchymal transition (EMT). In this study we show that TANK binding kinase-1 (TBK1) is a previously unknown mediator of platelet-induced EMT - a finding that suggests a possible role of TBK1 as a potential driver of metastatic disease. Using the two mammary epithelial cell lines Ep5 and MCF10A (M2), we show that co-culture with isolated platelets induced morphological as well as molecular features indicative of EMT, and that this is paralleled with activation of TBK1. Inhibiting TBK1 using siRNA suppressed platelet induced EMT in both Ep5 and MCF10A (M2) cells. Furthermore, platelet induced NF-κB signaling was suppressed after TBK1 knock down, suggesting that TBK1 is a crucial mediator of platelet-induced NF-κB signaling and subsequent EMT. Altogether, these results suggest that TBK1 contribute to tumor invasiveness and may hence be a driver of metastatic spread in mammary epithelial tumors.
platelets, cancer, TBK1, EMT
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-306182OAI: oai:DiVA.org:uu-306182DiVA: diva2:1039991