ERRα coordinates actin and focal adhesion dynamics

Cell migration depends on the dynamic organisation of the actin cytoskeleton and assembly and disassembly of focal adhesions (FAs). However, the precise mechanisms coordinating these processes remain poorly understood. We previously identified the oestrogen-related receptor α (ERRα) as a major regul...

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Bibliographic Details
Published in:Cancer gene therapy 2022-10, Vol.29 (10), p.1429-1438
Main Authors: Tribollet, Violaine, Cerutti, Catherine, Géloën, Alain, Berger, Emmanuelle, De Mets, Richard, Balland, Martial, Courchet, Julien, Vanacker, Jean-Marc, Forcet, Christelle
Format: Article
Language:English
Subjects:
Actin
Actin Depolymerizing Factors - metabolism
Actins - genetics
Actins - metabolism
Cancer
Cell adhesion
Cell adhesion & migration
Cell migration
Cell Movement - physiology
Cellular Biology
Cofilin
Cytoskeleton
Down-regulation
ERRalpha Estrogen-Related Receptor
Estrogens
Filaments
Focal Adhesions - metabolism
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Life Sciences
Protein Serine-Threonine Kinases
Receptors, Estrogen - genetics
Receptors, Estrogen - metabolism
RhoA protein
Subcellular Processes
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Summary:Cell migration depends on the dynamic organisation of the actin cytoskeleton and assembly and disassembly of focal adhesions (FAs). However, the precise mechanisms coordinating these processes remain poorly understood. We previously identified the oestrogen-related receptor α (ERRα) as a major regulator of cell migration. Here, we show that loss of ERRα leads to abnormal accumulation of actin filaments that is associated with an increased level of inactive form of the actin-depolymerising factor cofilin. We further show that ERRα depletion decreases cell adhesion and results in defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerisation defects resulting from ERRα silencing, but not cell adhesion. Instead, we found that MAP4K4 is a direct target of ERRα and down-regulation of its activity rescues cell adhesion and FA formation in the ERRα-depleted cells. Altogether, our results highlight a crucial role of ERRα in coordinating the dynamic of actin network and FAs through the independent regulation of the RhoA and MAP4K4 pathways.
ISSN:0929-1903
1476-5500
0929-1903
DOI:10.1038/s41417-022-00461-6