EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1alpha
Menée à l'aide de lignées cellulaires et de modèles murins, cette étude met en évidence un mécanisme par lequel le facteur EBF1, en contrôlant l'activité de la sous-unité alpha du facteur HIF1 pour éviter la mort cellulaire induite par la mitophagie, favorise la progression d'un cancer du sein triple négatif
Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1
α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.