Interference of Notch 1 inhibits the proliferation and invasion of breast cancer cells: Involvement of the β‑catenin signaling pathway

Abstract

Breast cancer is one of the most common types of carcinoma in humans. The aim of the present study was to identify the role of Notch 1 in the proliferation and invasion of human breast cancer cells. 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. An MTT assay was used to determine the viability of breast cancer cells. The optical density (OD)490 values were significantly decreased in Notch 1 short hairpin (sh)RNA‑transfected MCF‑7 and MDA‑MB‑231 cells, compared with the OD490 values in the negative control shRNA‑transfected cells. The MCF‑7 cells and MDA‑MB‑231 cells were also treated with increasing concentrations of MRK003, a Notch 1 inhibitor, for 24, 48 and 72 h, respectively. The inhibition rate was gradually increased in the MRK003‑treated cells in a time‑ and dose‑dependent manner. The invasive ability of the cells was determined using a Transwell migration assay. The migration ability was significantly decreased in the Notch 1‑transfected MCF‑7 cells and MDA‑MB‑231 cells. The molecular mechanism was examined, and the knockdown of Notch 1 significantly decreased the expression levels of β‑catenin, matrix metalloproteinase (MMP)‑2 and MMP‑9, and was also correlated with the downregulation of β‑catenin in the nucleus. In conclusion, Notch 1 was key in the progression of breast cancer, and knocking down the expression of Notch 1 significantly suppressed the proliferation and invasion of breast cancer cells. This provides novel clues for cancer therapy in human breast cancer.

TRIM67 Promotes the Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Positively Regulating the Notch Pathway

“…The role of the Notch pathway in cancers has been determined according to the effect of Notch pathway on cell proliferation, migration, and invasion [22][23][24][25][26]. In the present study, we demonstrated that TRIM67 overexpression can upregulate Notch1, Jagged1, and NICD.…”

Notch Signalling in Breast Development and Cancer

“…While most factors downstream of Notch increase the proliferative rate of the cell, Hes1 downregulates E2F1 expression which inhibits cell cycle progression (Hartman et al, 2009;Strom et al, 2009). Notch also activates key oncogenic signalling pathways with pleiotropic effects on cellular function including proliferation, such as c-Myc, Ras and Wnt (Mittal et al, 2009;Aster et al, 2017;Lai et al, 2018). Choy et al, 2017;Kong et al, 2018;Rui et al, 2018;Tu et al, 2019).…”

Analysis of changes in the expression of Notch1 and HES1 and the prognosis of osteosarcoma patients following surgery

“…The dysfunction of the Notch1 signaling pathway may lead to abnormal differentiation or undifferentiation, and may eventually lead to the malignant transformation of these cells. Of note, it has been revealed that changes in Notch1 signaling are associated with a number of human cancers (26)(27)(28); however, the role of Notch1 in osteosarcoma has yet not been elucidated. HES1 is a highly conserved basic helix-loop-helix transcription inhibitor, which mediates its biological effects by binding to N-cassettes (CACNAG) in the entire genome and recruiting chromatin modification factors to these sites (29,30).…”