RESUMEN
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.
Asunto(s)
Neoplasias de la Mama/patología , Quinasa I-kappa B , Macrófagos/citología , Proteínas Serina-Treonina Quinasas/metabolismo , Serina , Aminopiridinas/farmacología , Animales , Medios de Cultivo Condicionados , Células Epiteliales/patología , Femenino , Humanos , Quinasa I-kappa B/metabolismo , Inflamación , Glándulas Mamarias Humanas/patología , Ratones , Obesidad , Serina/biosíntesisRESUMEN
Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. It can be difficult to diagnose and symptoms might vary from being mild to chronic and progressive. Julie Holdsworth discusses the objectives of care management for patients with psoriatic arthritis and explains the rationale for the drugs used to treat this disease.