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TANK‐binding kinase 1 is a mediator of platelet‐induced EMT in mammary carcinoma cells
Author(s) -
Zhang Yanyu,
Unnithan Ragaseema Valsala Madhavan,
Hamidi Anahita,
Caja Laia,
Saupe Falk,
Moustakas Aristidis,
Cedervall Jessica,
Olsson Anna-Karin
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801936rrr
Subject(s) - mediator , mammary carcinoma , cancer research , platelet , chemistry , microbiology and biotechnology , kinase , carcinoma , biology , medicine , immunology
ABSTRACT Platelets can promote several stages of the metastatic process and thus contribute to malignant progression. As an example, platelets promote invasive properties of tumor cells by induction of epithelial to mesenchymal transition (EMT). In this study, we show that tumor necrosis factor receptor‐associated factor (TRAF) family member‐associated NF‐κB activator (TANK)‐binding kinase 1 (TBK1) is a previously unknown mediator of platelet‐induced EMT in mammary carcinoma cells. Coculture of 2 mammary carcinoma cell lines, Ep5 from mice and MCF10A(MII) from humans, with isolated platelets induced morphologic as well as molecular changes characteristic of EMT, which was paralleled with activation of TBK1. TBK1 depletion using small interfering RNA impaired platelet‐induced EMT in both Ep5 and MCF10A(MII) cells. Furthermore, platelet‐induced activation of the NF‐κB subunit p65 was suppressed after TBK1 knockdown, demonstrating that TBK1 mediates platelet‐induced NF‐κB signaling and EMT. Using an in vivo metastasis assay, we found that depletion of TBK1 from mammary carcinoma cells during in vitro preconditioning with platelets subsequently suppressed the formation of lung metastases in mice. Altogether, these results suggest that TBK1 contributes to tumor invasiveness and may be a driver of metastatic spread in breast cancer.—Zhang, Y., Unnithan, R. V. M., Hamidi, A., Caja, L., Saupe, F., Moustakas, A., Cedervall, J., Olsson, A.‐K. TANK‐binding kinase 1 is a mediator of platelet‐induced EMT in mammary carcinoma cells. FASEB J. 33, 7822–7832 (2019). www.fasebj.org