Yes-associated protein 1 promotes the metastasis of U251 glioma cells by upregulating Jagged-1 expression and activating the Notch signal pathway

Yes-associated protein 1 (YAP1) is overexpressed in a number of human cancer types as an oncogene and takes part in processes of tumor cell proliferation, apoptosis and metastasis. The Notch pathway also has an important role in tumorigenesis and progression. However, the possible association between YAP1 and Notch signaling in glioma has remained to be determined. The present study verified the high expression of YAP1, Jagged 1 (JAG1), NOTCH1 and HES1 in the U251 glioma cell line via reverse-transcription quantitative polymerase chain reaction and western blot analysis. The effects of YAP1 knockdown with small interfering RNA and overexpression of JAG1 or FIES1 with the respective recombinant plasmid on the expression of these proteins in U251 cells were also assessed. The expression of JAG1, intracellular domain of the notch protein and HES1 was reduced upon knockdown of YAP1, but the expression of YAP1 was not affected by overexpression of JAG1 or HES1. Furthermore, a Transwell assay was used to assess the migration of U251 cells in vitro following knockdown of YAP1 gene and/or overexpression of JAG1 or HES1. U251 cell migration was decreased following YAP1 knockdown, which was compensated by overexpression of JAG1 or HES1. Overexpression of YAP1 upregulated JAG1 to activate Notch signaling in U251 cells and YAP1-dependent activity of JAG1, and the Notch pathway promoted the metastasis of U251 cells in vitro. This suggested that YAP1 promoted the metastasis of U251 cells via upregulating JAG1 and activating Notch signaling.