Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

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Bibtex

@article{4d7f4c99319c4aea84cc9b3303a3f0bb,
title = "Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression",
abstract = "Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-beta/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1(ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.",
keywords = "lymphangiogenesis, angiogenesis, blood vascular endothelial cells",
author = "Yasuhiro Yoshimatsu and Lee, {Yulia G.} and Yuichi Akatsu and Luna Taguchi and Suzuki, {Hiroshi I.} and Cunha, {Sara I.} and Kazuichi Maruyama and Yuka Suzuki and Tomoko Yamazaki and Akihiro Katsura and Oh, {S. Paul} and Zimmers, {Teresa A.} and Se-Jin Lee and Kristian Pietras and Koh, {Gou Young} and Kohei Miyazono and Tetsuro Watabe",
note = "The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)",
year = "2013",
doi = "10.1073/pnas.1310479110",
language = "English",
volume = "110",
pages = "18940--18945",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
publisher = "National Acad Sciences",
number = "47",

}