Sex Hormone Estrone Sulfate Serendipitously Downregulates Intercellular Tunneling Nanotube Conduits, EMT, and Migration in Breast and Pancreatic Cancer Cells

Aim

Estrone (E1) is of particular interest as most breast cancers are diagnosed after menopause, the period in which E1 becomes the dominant estrogen. Triple-negative breast cancer (TNBC) is a highly invasive cancer that lacks hormone receptors for estrogen (ER), progesterone (PR), and HER2 (human epidermal growth factor receptor-2). TNBC management remains clinically challenging despite recent advances in targeted and immunotherapeutic approaches. This study investigated the effects of the estrogen hormone estrone sulfate (E1S) on cancer cells. Here, E1S engages in non-classical biased G protein-coupled estrogen receptor (GPER) signaling in TNBC MDA-MB-231 cells, estrogen receptor-positive MCF-7 breast cancer cells, and pancreatic PANC-1 cancer cells, which express estrogen, progesterone, and androgen receptors.