Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/69343
Title: BMP9 is a proliferative and survival factor for human hepatocellular carcinoma cells
Author: Herrera, Blanca
García Álvaro, María
Cruz, Silvia
Walsh, Peter
Fernández, Margarita
Roncero, Cesáreo
Fabregat Romero, Isabel
Sánchez, Aránzazu
Inman, Gareth J.
Keywords: Cèl·lules canceroses
Càncer de fetge
Cancer cells
Liver cancer
Issue Date: 2013
Publisher: Public Library of Science (PLoS)
Abstract: TGF-β family members play a relevant role in tumorigenic processes, including hepatocellular carcinoma (HCC), but a specific implication of the Bone Morphogenetic Protein (BMP) subfamily is still unknown. Although originally isolated from fetal liver, little is known about BMP9, a BMP family member, and its role in liver physiology and pathology. Our results show that BMP9 promotes growth in HCC cells, but not in immortalized human hepatocytes. In the liver cancer cell line HepG2, BMP9 triggers Smad1,5,8 phosphorylation and inhibitor of DNA binding 1 (Id1) expression up- regulation. Importantly, by using chemical inhibitors, ligand trap and gene silencing approaches we demonstrate that HepG2 cells autocrinely produce BMP9 that supports their proliferation and anchorage independent growth. Additionally, our data reveal that in HepG2 cells BMP9 triggers cell cycle progression, and strikingly, completely abolishes the increase in the percentage of apoptotic cells induced by long-term incubation in low serum. Collectively, our data unveil a dual role for BMP9, both promoting a proliferative response and exerting a remarkable anti-apoptotic function in HepG2 cells, which result in a robust BMP9 effect on liver cancer cell growth. Finally, we show that BMP9 expression is increased in 40% of human HCC tissues compared with normal human liver as revealed by immunohistochemistry analysis, suggesting that BMP9 signaling may be relevant during hepatocarcinogenesis in vivo. Our findings provide new clues for a better understanding of BMPs contribution, and in particular BMP9, in HCC pathogenesis that may result in the development of effective and targeted therapeutic interventions.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0069535
It is part of: PLoS One, 2013, vol. 8, num. 7, p. e69535
Related resource: http://dx.doi.org/10.1371/journal.pone.0069535
URI: http://hdl.handle.net/2445/69343
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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