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TANK-binding kinase 1 is a mediator of platelet-induced EMT in mammary carcinoma cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Govt Arts Coll, Thiruvananthapuram, Kerala, India.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-8786-8763
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2019 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, no 7, p. 7822-7832Article in journal (Refereed) Published
Abstract [en]

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-kappa B 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-kappa B subunit p65 was suppressed after TBK1 knockdown, demonstrating that TBK1 mediates platelet-induced NF-kappa B 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.

Place, publisher, year, edition, pages
2019. Vol. 33, no 7, p. 7822-7832
Keywords [en]
platelets, cancer, TBK1, NF-kappa B, metastasis
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-392047DOI: 10.1096/fj.201801936RRRISI: 000476234700004PubMedID: 30912981OAI: oai:DiVA.org:uu-392047DiVA, id: diva2:1349850
Funder
Swedish Research Council, 2016-03036Swedish Cancer Society, CAN 2017/522Swedish Society of Medicine, SLS-683851
Note

Ragaseema Valsala Madhavan Unnithan and Anahita Hamidi contributed equally to this work.

Jessica Cedervall and Anna-Karin Olsson contributed equally to this work.

Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-09-10Bibliographically approved

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Zhang, YanyuValsala Madhavan Unnithan, RagaseemaHamidi, AnahitaCaja, LaiaSaupe, FalkMoustakas, AristidisCedervall, JessicaOlsson, Anna-Karin

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Zhang, YanyuValsala Madhavan Unnithan, RagaseemaHamidi, AnahitaCaja, LaiaSaupe, FalkMoustakas, AristidisCedervall, JessicaOlsson, Anna-Karin
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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLab
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