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http://hdl.handle.net/2445/180977
Title: | The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice |
Author: | Ribera, Jordi Portolés, Irene Córdoba Jover, Bernat Rodríguez Vita, Juan Casals Mercadal, Gregori González de la Presa, Bernardino Graupera i Garcia-Milà, Mariona Solsona Vilarrasa, Estel Garcia Ruiz, Carmen Fernández Checa Torres, José Carlos Soria, Guadalupe Tudela Fernández, Raúl Esteve Codina, Anna Espadas, Guadalupe Sabidó Aguadé, Eduard Jiménez, Wladimiro Sessa, William C. Morales Ruiz, Manuel |
Keywords: | Enzims Metàstasi Enzymes Metastasis |
Issue Date: | 15-Oct-2021 |
Publisher: | Springer Nature |
Abstract: | DHX15 is a downstream substrate for Akt1, which is involved in key cellular processes affecting vascular biology. Here, we explored the vascular regulatory function of DHX15. Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15 / zebrafish also showed downregulation of VEGF-C and reduced formation of lymphatic structures during development. DHX15+/− mice depicted lower vascular density and impaired lymphatic function postnatally. RNAseq and proteome analysis of DHX15 silenced endothelial cells revealed differential expression of genes involved in the metabolism of ATP biosynthesis. The validation of these results demonstrated a lower activity of the Complex I in the mitochondrial membrane of endothelial cells, resulting in lower intracellular ATP production and lower oxygen consumption. After injection of syngeneic LLC1 tumor cells, DHX15+/− mice showed partially inhibited primary tumor growth and reduced lung metastasis. Our results revealed an important role of DHX15 in vascular physiology and pave a new way to explore its potential use as a therapeutical target for metastasis treatment. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s42003-021-02722-w |
It is part of: | Communications Biology, 2021, vol. 4, p. 1192 |
URI: | http://hdl.handle.net/2445/180977 |
Related resource: | https://doi.org/10.1038/s42003-021-02722-w |
ISSN: | 2399-3642 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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