Plasminogen activator uPA is a direct transcriptional target of the JAG1-Notch receptor signaling pathway in breast cancer.

Aberrant activation of the Notch receptor signaling pathway and overexpression of the Notch ligand JAG1 are associated with poor outcome in breast cancer. The plasminogen activator system, which includes urokinase-type plasminogen activator (uPA), has been validated as a marker of recurrence, high metastasis risk and death in breast malignancy. By using microarray profiling of breast cancer cell lines that had undergone siRNA-mediated abrogation of Notch signaling we uncovered a link between activated Notch signaling and uPA expression. An association between elevated expression of the Notch ligand JAG1, uPA, and the basal-like breast cancer subtype was confirmed in breast cancer cell lines. The association between JAG1 and uPA expression persisted in a survey of primary carcinomas of the breast. We found that Notch knockdown reduced transcription of uPA and phenocopied uPA knockdown in breast cancer cells. Through mutational analysis we identified a CBF-1 binding site in the uPA promoter that is required for direct transcriptional regulation by Notch. These data suggest that JAG1-induced Notch activation results in breast cancer progression through upregulation of the plasminogen activator system, directly linking these 2 important pathways of poor prognosis.

Shimizu M ，Cohen B ，Goldvasser P ，Berman H ，Virtanen C ，Reedijk M ... -  《-》

Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer.

Cohen B ，Shimizu M ，Izrailit J ，Ng NF ，Buchman Y ，Pan JG ，Dering J ，Reedijk M ... -  《-》

Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling.

Nishina S ，Shiraha H ，Nakanishi Y ，Tanaka S ，Matsubara M ，Takaoka N ，Uemura M ，Horiguchi S ，Kataoka J ，Iwamuro M ，Yagi T ，Yamamoto K ... -  《-》

Specific knockdown of uPA/uPAR attenuates invasion in glioblastoma cells and xenografts by inhibition of cleavage and trafficking of Notch -1 receptor.

Raghu H ，Gondi CS ，Dinh DH ，Gujrati M ，Rao JS ... -  《Molecular Cancer》

Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells.

Katoh M ，Katoh M 《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》