IL6/STAT3 Signaling Hijacks Estrogen Receptor alpha
Menée à l'aide de modèles murins de cancer du sein ER+, cette étude met en évidence un mécanisme par lequel la voie de signalisation IL6/STAT3 favorise le processus métastatique via les mêmes régions amplificatrices que celles utilisées par la voie de signalisation ER/FOXA1
The cytokine interleukin-6 (IL6) and its downstream effector STAT3 constitute a key oncogenic pathway, which has been thought to be functionally connected to estrogen receptor α (ER) in breast cancer. We demonstrate that IL6/STAT3 signaling drives metastasis in ER+ breast cancer independent of ER. STAT3 hijacks a subset of ER enhancers to drive a distinct transcriptional program. Although these enhancers are shared by both STAT3 and ER, IL6/STAT3 activity is refractory to standard ER-targeted therapies. Instead, inhibition of STAT3 activity using the JAK inhibitor ruxolitinib decreases breast cancer invasion in vivo. Therefore, IL6/STAT3 and ER oncogenic pathways are functionally decoupled, highlighting the potential of IL6/STAT3-targeted therapies in ER+ breast cancer.
Cancer Cell 2020