LIVE OR DIE: In breast cancer cells expressing estrogen receptor-α (ER-α), the inhibition of the autophagy gene ATG7 (top panel) allows an apoptosis transcription factor, IRF1, to lead the cancer cell to die upon antiestrogen therapy, which outcompetes estrogen for binding the receptor. When IRF1 is knocked down (lower panel), antiestrogens are less potent as the activity of ATG7 and another autophagy factor, BECN1, aids in cell survival by supporting autophagy.© EVAN OTO/SCIENCE SOURCE
The paper
J.L. Schwartz-Roberts et al., “Interferon regulatory factor-1 signaling regulates the switch between autophagy and apoptosis to determine breast cancer cell fate,” Cancer Res, 75:783-91, 2015.
About 70 percent of breast cancers express estrogen receptor-α (ER-α). In these cancers, the receptor binds estrogen then translocates to the nucleus, where it upregulates genes leading to cancer growth. Antiestrogen drugs, which compete with endogenous estrogen, can prevent this from happening. When they work, antiestrogen therapies lead breast cancer cells to undergo apoptosis, often through a signaling pathway involving the transcription factor interferon regulatory factor-1 (IRF1). Unfortunately, most breast cancers eventually become resistant to such drugs.
Previous studies showed that IRF1 was downregulated in antiestrogen-resistant breast cancer cell lines, suggesting that it was the loss of IRF1’s ...
