Huaier polysaccharide inhibits the stem-like characteristics of ERα-36triple negative breast cancer cells via inactivation of the ERα-36 signaling pathway.
Int J Biol Sci. 2019 ;15(7):1358-1367. Epub 2019 May 20. PMID: 31337967
Triple negative breast cancer (TNBC) is a highly aggressive cancer and lack of targeting therapies. It is believed that the breast cancer stem cells (BCSCs) are responsible for the aggressive characteristics of TNBC. Hence, developing BCSC-targeting agents may provide new therapeutic strategies for the patients. Huaier polysaccharide (HP), an active ingredient extracted from the mushroomMurr, has been widely used in clinical anti-cancer treatments in China. Here we demonstrated that HP could target BCSCs in TNBC cells, resulting in decreased mammosphere formation, downregulated expression of stem-related genes and reduced proportion of aldehyde dehydrogenase positive cellsand inhibited xenograft tumor formation. Mechanically, HP markedly reduced the expression of estrogen receptorα-36 (ERα-36), a recently identified subtype of estrogen receptor α, and attenuated ERα-36-mediated activation of AKT/β-catenin signaling in ERα-36TNBC cells. This study provides a new insight into the mechanism of HP on BCSC-targeting therapy and new ideas for comprehensive treatment strategies for TNBC.