ERRα regulates the growth of triple-negative breast cancer cells via S6K1-dependent mechanism

• DOI: 10.1038/sigtrans.2017.35
• Publication Date: 2017-08-25T08:59:20Z
• Authors: Adi Y Berman; Subrata Manna; Naomi S Schwartz; Yardena E Katz; Yang Sun; Catherine A Behrmann; Jane J Yu; David R Plas; Anya Alayev; Marina K Holz
• Keywords: Triple-negative breast cancer

Estrogen-related receptor alpha (ERRα) is an orphan nuclear factor that a master regulator of cellular energy metabolism. ERRα overexpressed in variety tumors, including ovarian, prostate, colorectal, cervical and breast, associated with more aggressive tumor worse outcome. In breast cancer, specifically, high expression increased rate recurrence poor prognosis. Because the common functions mTORC1/S6K1 signaling pathway regulation metabolism cancer pathogenesis, we focused on investigating biochemical relationship between S6K1. We found negatively regulates S6K1 by directly binding to its promoter. Downregulation sensitized ERα-negative cells inhibitors. Therefore, our results show combinatorial inhibition may have clinical utility treatment triple-negative warrants further investigation.