Overexpression of BMP9 promotes ovarian cancer progression via Notch1 signaling

Lijuan Yang, Yingying Bai, Chaihong Zhang, Junhong Du, Yuemei Cheng, Qinganzi Wang, Bo Zhang,  Yongxiu Yang

Abstract:

Cell proliferation and migration play important parts in ovarian cancer progression. BMP9, as one of the members of the TGF-β superfamily and BMP family, plays a diverse and significant array of biological roles, including cell differentiation, proliferation, apoptosis, tumorigenesis, and metabolism. However, the role and mechanism of BMP9 in ovarian cancer progression remains uncertain. We found that the expression of BMP9 was increased in human ovarian cancer cell lines, which induced Notch1 intracellular domain (NICD1) accumulation. And we also found the expression abundance of BMP9 is low in ovarian cancer cells. Thus, we generated recombinant adenoviruses overexpressing BMP9 to perform the research. We found that overexpression of BMP9 promoted ovarian cancer cell proliferative viability, cell cycle progression, cell migration in vitro, and accelerated subcutaneous tumor growth in vivo, which was inhibited by dominant-negative mutant Notch1 recombinant adenoviruses. Besides, we also demonstrated that silencing of BMP9 by recombinant adenoviruses inhibited ovarian cancer cell viability and migration in vitro. Additionally, BMP9-induced ovarian cancer cell progression also involved the elevation of HES2, c-Myc, MMP9, and Cyclin D1, as well as repressed expression of p27. Together, these results revealed that BMP9 acts as a promoting factor in ovarian cancer progression, and overexpression of BMP9 promotes ovarian cancer progression and growth via Notch1 signaling. Thereby our research may provide new insight into the pathogenesis of ovarian cancer and BMP9-Notch1 signaling may serve as a novel therapeutic target axis for ovarian cancer treatment.