title: Notch1 is involved in migration and invasion of human breast cancer cells.
abstract: The Notch pathway displays several functions related to tumor progression. Breast carcinomas commonly express Notch1, Notch2, Notch3 and Notch4 at variable levels and these are mainly involved in differentiation, proliferation and survival. Notch1 can also induce the invasion of breast cancer cells. However, the precise role and mechanism of Notch1 in tumor invasion remains unclear. In this report, we used small interference RNA technology to knock down the expression of Notch1, resulting in reduced migration and invasion of breast cancer cells. Meanwhile, F-actin polymerization, which is essential for cellular generation of the forces needed for motility, was also impaired in Notch1 knockdown cells. We further investigated the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteases-2 (MMP-2) and MMP-9, and found that the expression of functional EMMPRIN and MMP-2 was significantly decreased in Notch1 knockdown cells, while the expression of MMP-9 was constant. Additionally, the silencing of Notch1 expression likewise impaired cell-to-matrix and cell-to-cell adhesion. Western blotting results showed that reduction of Notch1 levels impacted the phosphorylation of PAK, phosphorylation of Akt, phosphorylation of FAK, the phosphorylation of integrin β1, ICAM-1 and β-catenin. Collectively, these findings suggest that targeting Notch1 has important therapeutic value in breast cancer.
authors.affiliation: Central Laboratory of Oncology Department, Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Ma
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1