Deregulation of transcriptional and epigenetic mechanisms is a hallmark of cancer development and progression. In breast cancer, the two steroid hormone receptors, estrogen receptor α and glucocorticoid receptor, are key transcriptional drivers of cancer biology. A key function of these receptors is to induce expression of the oncoprotein MYC, which drives multiple hallmarks of cancer progression. MYC is known to promote oncogenic transcription by binding to active promoters. In addition, MYC has also been shown to invade distal enhancers when expressed at oncogenic levels, but this enhancer binding has been thought to have low gene-regulatory potential. 

We have recently identified a feedforward loop involving co-binding of steroid hormone receptors and MYC at enhancers in breast cancer. We demonstrate that MYC directly regulates the activity of these enhancers to promote cancer progression. Interestingly, the mechanistic role of MYC at enhancers is different from its role at promoters, and we propose that MYC enhancer activity represents a potential therapeutic vulnerability in cancer. In this talk, I will present our most recent findings on the function of steroid hormone receptors and MYC at transcriptional enhancers in cancer.