Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway

Abstract: During obesity, macrophages infiltrate the breast tissue leading to low‐grade chronic inflammation, a factor considered responsible for the higher risk of breast cancer associated with obesity. Here, we formally demonstrate that breast epithelial cells acquire malignant properties when exposed to medium conditioned by macrophages derived from human healthy donors. These effects were mediated by the breast cancer oncogene IKKε and its downstream target—the serine biosynthesis pathway as demonstrated by genetic or pharmacological tools. Furthermore, amlexanox, an FDA‐approved drug targeting IKKε and its homologue TBK1, delayed in vivo tumour formation in a combined genetic mouse model of breast cancer and high‐fat diet‐induced obesity/inflammation. Finally, in human breast cancer tissues, we validated the link between inflammation–IKKε and alteration of cellular metabolism. Altogether, we identified a pathway connecting obesity‐driven inflammation to breast cancer and a potential therapeutic strategy to reduce the risk of breast cancer associated with obesity.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway ; volume:12 ; number:2 ; year:2020 ; extent:20 ; EMBO molecular medicine / European Molecular Biology Organization ; 12, Heft 2 (2020) (gesamt 20)

Contributors, Places and Time

• Creator: Wilcz‐Villega, Ewa ; Carter, Edward ; Ironside, Alastair ; Xu, Ruoyan ; Mataloni, Isabella ; Holdsworth, Julie ; Jones, William ; Moreno Béjar, Rocío ; Uhlik, Lukas ; Bentham, Robert B. ; Godinho, Susana A. ; Dalli, Jesmond ; Grose, Richard ; Szabadkai, Gyorgy ; Jones, Louise ; Hodivala‐Dilke, Kairbaan ; Bianchi, Katiuscia

Further information

• DOI: 10.15252/emmm.201910491
• URN: urn:nbn:de:101:1-2022062408231677889600
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:20 AM CEST