title: Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.
abstract: Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Juliette
authors.initials: J
authors.lastname: Sailland
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Violaine
authors.initials: V
authors.lastname: Tribollet
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Christelle
authors.initials: C
authors.lastname: Forcet
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Billon
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Bruno
authors.initials: B
authors.lastname: Barenton
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Julie
authors.initials: J
authors.lastname: Carnesecchi
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Alice
authors.initials: A
authors.lastname: Bachmann
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France;
authors.forename: Karine Cécile
authors.initials: KC
authors.lastname: Gauthier
authors.affiliation: Cancer and Inflammation Program, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; and.
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Rosalind and Morris Goodman Cancer Centre, McGill University, Montréal, QC, Canada H3A 1A3.
authors.forename: Vincent
authors.initials: V
authors.lastname: Giguère
authors.affiliation: Cancer and Inflammation Program, School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; and.
authors.forename: Franky L
authors.initials: FL
authors.lastname: Chan
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, Ecole Normale Supérieure de Lyon, 69007 Lyon, France; jean-marc.vanacker@ens-lyon.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vanacker
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D044842:Cullin Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D014945:Wound Healing; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D044842:Cullin Proteins; D011506:Proteins; D011960:Receptors, Estrogen; D020742:rhoA GTP-Binding Protein; D000097983:ERRalpha Estrogen-Related Receptor; C503645:CUL3 protein, human; C115968:TNFAIP1 protein, human; C066737:RHOA protein, human
keywords: ERR; RhoA; cell migration; nuclear receptor; protein stability