In vivo and in vitro experiments both showed that SNHG7 targeted miR-34a and promoted epithelial-to-mesenchymal transition (EMT) initiation and the Notch-1 pathway in breast cancer.
Moreover, patients with HER2-positive breast cancers expressing high Notch1 activation and low EPHA5 expression could be the best candidates for anti-Notch1 therapy.-Li, Y., Chu, J., Feng, W., Yang, M., Zhang, Y., Zhang, Y., Qin, Y., Xu, J., Li, J., Vasilatos, S. N., Fu, Z., Huang, Y., Yin, Y. EPHA5 mediates trastuzumab resistance in HER2-positive breast cancers through regulating cancer stem cell-like properties.
Subsequently, Notch1 was identified as the functional target of miR‑449a, and the overexpression of circRNA-000911 in breast cancer elevated Notch1 expression.
Inhibition of MEK1/2-ERK1/2 signaling in trastuzumab-resistant breast cancer cells mimics effects of Notch-1 knockdown on bulk cell proliferation and BCSC survival.
We show that the miR-106b-25 cluster upregulates NOTCH1 in multiple breast cancer cell lines, representing both estrogen receptor (ER+) and triple negative breast cancer (TNBC) through direct repression of the E3 ubiquitin ligase, NEDD4L.
Resistance to anti-HER2 therapy in HER2<sup>+</sup> breast cancer requires NOTCH1, and that combination of trastuzumab and a gamma secretase inhibitor (GSI) prevents tumor relapse in xenograft models.<b>Experimental Design:</b> The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates NOTCH-dependent CSC survival and tumor initiation.<b>Results:</b> Lapatinib-mediated HER2 inhibition shifts the population of HER2<sup>+</sup> breast cancer cells from low membrane JAGGED1 expression to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population.
Firstly, the levels of Notch 1 were determined by western blot analysis in breast cancer cell lines, and the results revealed that the expression levels of Notch 1 were markedly higher in MDA‑MB‑231 and MCF‑7 cells, and lower in MCF‑10A cells, compared with human mammary epithelial cells.
Furthermore, modulation of KRT19-mediated regulation of NUMB and NOTCH1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133<sup>high</sup>/CXCR4<sup>high</sup>/ALDH1<sup>high</sup> cancer stem-like cells (CSLCs), which showed very low KRT19 and high NOTCH1 expression.
These data suggest that the putative involvement of NOTCH1 as a tumor-promoting gene in breast cancer may depend on its lack of regulation in cancer, whereas its involvement in normal lumen formation requires activation of its expression, and subsequently, inhibition of its signaling.
OIP5 over-expression inhibited hsa-miR-139-5p expression, antagonized its functions and led to the de-repression of its endogenous target NOTCH1, which was a core oncogene in promoting breast cancer progression.
Notch1 and ATM activation are inversely correlated in human breast cancers, and inactivation of ATM by Notch1 contributes to the survival of Notch1-driven leukemia cells upon DNA damage.
Notch1 silencing reversed the spontaneous EMT process and inhibited the migration and invasion of breast cancer cells and the growth of xenograft breast cancers.