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
  • Lymphatic System/pathology*
  • Neoplasm Metastasis*
  • Zebrafish/embryology
  • Energy Metabolism*
  • Embryo, Mammalian/metabolism
  • RNA Helicases/deficiency*
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Neoplasms
  • Mice
  • Endothelium/metabolism
  • Animals
  • Mice, Transgenic/embryology
(all 13)
PubMed
34654883 Full text @ Commun Biol
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
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
idb1
    Small Deletion
    la116TgTransgenic Insertion
      zf3396TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        dhx15CRISPR15-dhx15CRISPR
        1 - 1 of 1
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        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        GFPEFGGFP
        RFPEFGRFP
        1 - 2 of 2
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        Mapping
        No data available