Regulation of Breast Cancer Stem Cell Activity by Signaling through the Notch4 Receptor

Abstract

Notch receptor signaling pathways play an important role not only in normal breast development but also in breast cancer development and progression.

Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation

“…Our data demonstrate an essential cell autonomous role of Notch1 in breast CSCs expansion. Harrison et al 42 has reported that Notch4 also affects breast CSCs. They performed knockdown of Notch paralog (Notch1 and Notch4) using both ESA þ / CD44 þ /CD24 low and mammosphere prepared from MCF-7 cells, although Notch ICD overexpression was not examined.…”

Epithelial-to-mesenchymal transition (EMT) confers primary resistance to trastuzumab (Herceptin)

“…The formation of primary mammospheres is a reliable in vitro assay to measure stem cell/early progenitor activity and, therefore, to demonstrate the presence of a stem cell population. [50][51][52][53] Because CD44 + CD24 -/ low cells have repeatedly been designated as highly tumorigenic the anti-proliferative activity of trastuzumab against the trastuzumab-refractory JIMT1 cells.…”

NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells

“…Later, numerous studies established that the NOTCH1 signaling pathway plays a role in breast cancer development (22). Recently, many reports have suggested a function of the NOTCH signaling pathway in promoting self-renewal of mammary stem cells and breast cancer stem cells (23)(24)(25)(26). Harrison et al reported that pharmacologic or genetic inhibition of NOTCH reduced stem cell activity in vitro and tumor formation in vivo.…”