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TWEAK promotes migration and invasion in MEFs through a mechanism dependent on ERKs activation and Fibulin 3 down-regulation.

Authors
  • Sequera, Celia1, 2
  • Vázquez-Carballo, Ana1, 2
  • Arechederra, María1, 2
  • Fernández-Veledo, Sonia3, 4
  • Porras, Almudena1, 2
  • 1 Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular II, Universidad Complutense de Madrid, Madrid, Spain. , (Spain)
  • 2 Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. , (Spain)
  • 3 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. , (Spain)
  • 4 Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain. , (Spain)
Type
Published Article
Journal
Journal of Cellular Physiology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2018
Volume
233
Issue
2
Pages
968–978
Identifiers
DOI: 10.1002/jcp.25942
PMID: 28383766
Source
Medline
Keywords
License
Unknown

Abstract

TWEAK regulates multiple physio-pathological processes in fibroblasts such as fibrosis. It also induces migration and invasion in tumors and it can activate p38 MAPK in various cell types. Moreover, p38α MAPK promotes migration and invasion in several cancer cells types and in mouse embryonic fibroblasts (MEFs). However, it remains unknown if TWEAK could promote migration in fibroblasts and whether p38α MAPK might play a role. Our results reveal that TWEAK activates ERKs, Akt, and p38α/β MAPKs and reduces secreted Fibulin 3 in MEFs. TWEAK also increases migration and invasion in wt and p38α deficient MEFs, which indicates that p38α MAPK is not required to mediate these effects. In contrast, ERKs inhibition significantly decreases TWEAK-induced migration and Fibulin 3 knock-down mimics TWEAK effect. These results indicate that both ERKs activation and Fibulin 3 down-regulation would contribute to mediate TWEAK pro-migratory effect. In fact, the additional regulation of ERKs and/or p38β as a consequence of Fibulin 3 decrease might be also involved in the pro-migratory effect of TWEAK in MEFs. In conclusion, our studies uncover novel mechanisms by which TWEAK would favor tissue repair by promoting fibroblasts migration.

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