PUBLICATION
The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice
- Authors
- Ribera, J., Portolés, I., Córdoba-Jover, B., Rodríguez-Vita, J., Casals, G., González-de la Presa, B., Graupera, M., Solsona-Vilarrasa, E., Garcia-Ruiz, C., Fernández-Checa, J.C., Soria, G., Tudela, R., Esteve-Codina, A., Espadas, G., Sabidó, E., Jiménez, W., C Sessa, W., Morales-Ruiz, M.
- ID
- ZDB-PUB-211022-4
- Date
- 2021
- Source
- Communications biology 4: 1192 (Journal)
- Registered Authors
- Casals, Gregori, Morales-Ruiz, Manuel, Ribera, Jordi
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Mammalian/metabolism
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Endothelium/metabolism
- Energy Metabolism*
- Lymphatic System/pathology*
- Mice
- Mice, Transgenic/embryology
- Neoplasm Metastasis*
- Neoplasms
- RNA Helicases/deficiency*
- Zebrafish/embryology
- PubMed
- 34654883 Full text @ Commun Biol
Citation
Ribera, J., Portolés, I., Córdoba-Jover, B., Rodríguez-Vita, J., Casals, G., González-de la Presa, B., Graupera, M., Solsona-Vilarrasa, E., Garcia-Ruiz, C., Fernández-Checa, J.C., Soria, G., Tudela, R., Esteve-Codina, A., Espadas, G., Sabidó, E., Jiménez, W., C Sessa, W., Morales-Ruiz, M. (2021) The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice. Communications biology. 4:1192.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping