17ß-estradiol promotes metastasis in patients with triple-negative breast cancer. A cell culture and mouse model study demonstrated that this process may be mediated by the calpain/YAP/ß-catenin signaling axis.
The absence of estrogen and progesterone receptors and human epidermal growth factor receptor-2 characterizes triple-negative breast cancer (TNBC) cells. The estrogen 17ß-estradiol, or E2, promotes the proliferation of estrogen receptor (ER)-positive breast cancer cells, which enhances the malignant proliferation of these tumors.
Previous studies have demonstrated E2-mediated regulation of expression and activation of ß-catenin, which mediates metastasis in TNBC. This cell culture study explored the underlying mechanism of ß-catenin in E2-mediated metastasis in TNBC. The findings are published in the journal PloS One.
Proliferation, Migration, and Invasion of Triple-Negative Breast Cancer
At 10–100 nM, E2 was found to promote the proliferation of TNBC cells, with the greatest effect being observed at a 30 nM concentration. At this concentration, E2 enhanced the migration and invasion of TNBC cells.
ß-Catenin Expression and Activation in Triple-Negative Breast Cancer
E2 upregulated the expression levels of ß-catenin protein in TNBC cells, including increased protein levels in the nucleus. E2 increased the activity of calpain and downregulated the expression of calpastatin, which is a calpain inhibitory protein. Calpeptin suppressed the accumulation of E2-induced ß-catenin in the nucleus of TNBC cells.
Metastasis via Calpain/YAP/ß-Catenin Axis
The inhibition of calpain, ß-catenin, or yes-associated protein (YAP) inhibited E2-mediated proliferation, migration, and invasion of TNBC cells. Suppression of the calpain/ß-catenin pathway also inhibited E2-mediated lung metastasis in a mouse model.
Source:
Niu, X., Wang, J., Liu, J., Yu, Q., & Ci, M. (2024). 17β-Estradiol promotes metastasis in triple-negative breast cancer through the Calpain/YAP/β-catenin signaling axis. PloS One, 19(3), e0298184. https://doi.org/10.1371/journal.pone.0298184
