BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

International Journal of Molecular Sciences
María García-ÁlvaroBlanca Herrera

Abstract

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling p...Continue Reading

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Citations

May 12, 2018·Liver International : Official Journal of the International Association for the Study of the Liver·Annalisa AddanteAránzazu Sánchez
Jun 27, 2018·International Journal of Molecular Sciences·Mengyao LiuYan Zhang
Jan 26, 2016·The FEBS Journal·Isabel FabregatUNKNOWN IT-LIVER Consortium
Apr 13, 2018·International Journal of Molecular Sciences·Liyao GouYan Zhang
May 22, 2021·Molecular and Cellular Biochemistry·Qian-Qian JiangKe-Shu Xu
Jul 9, 2021·Experimental Biology and Medicine·Yu HouYan Zhang

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Methods Mentioned

BETA
transgenic
flow cytometry
transfection
ELISA
electrophoresis
PCR

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