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Int. J. Mol. Sci. 2015, 16(9), 20431-20448;

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

Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University of Madrid. San Carlos Clinical Hospital Health Research Institute (IdISSC), Plaza Ramón y Cajal S/N, Madrid 28040, Spain
Bellvitge Biomedical Research Institute (IDIBELL) and University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona 08908, Spain
Author to whom correspondence should be addressed.
Academic Editor: Johannes Haybaeck
Received: 28 April 2015 / Revised: 31 July 2015 / Accepted: 18 August 2015 / Published: 28 August 2015
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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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 pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells. View Full-Text
Keywords: BMP9; non-Smad; apoptosis; liver cancer; p38MAPK; PI3K BMP9; non-Smad; apoptosis; liver cancer; p38MAPK; PI3K

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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García-Álvaro, M.; Addante, A.; Roncero, C.; Fernández, M.; Fabregat, I.; Sánchez, A.; Herrera, B. BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation. Int. J. Mol. Sci. 2015, 16, 20431-20448.

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