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Artículo

GEF-H1 drives breast cancer cells to tumor progression

Fernández Chávez, LucíaIcon ; Schweitzer, KarenIcon ; Alonso, Exequiel GonzaloIcon ; Ferronato, María JuliaIcon ; Fermento, María EugeniaIcon ; Alonso, Eliana NoeliaIcon ; Facchinetti, Maria MartaIcon ; Curino, Alejandro CarlosIcon ; Colo, Georgina PamelaIcon
Fecha de publicación: 26/03/2025
Editorial: Elsevier Science
Revista: Biochimica et Biophysica Acta - Molecular Basis of Disease
ISSN: 0925-4439
e-ISSN: 1879-260X
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Rho GTPases are involved in several biological processes, including cytoskeletal remodeling, gene transcription, cell proliferation and differentiation. Dysregulation of Rho GTPases activity can lead to enhanced tumor cell proliferation and metastasis. Rho guanine nucleotide exchange factor-H1 (GEFsingle bondH1) is a RhoA activator that is associated with microtubules (MT) and its localization and activity are regulated, in part, by MT and fibronectin-binding integrins. Our findings showed that GEF-H1 expression is significantly higher in human breast cancer biopsies than in normal tissues. Moreover, patients with increased GEF-H1 expression had a lower survival rate and a higher incidence of metastasis. We generated a GEF-H1 knockout (KO) breast cancer cell line and observed a significant reduction in the number of focal adhesions, formation of stress fibers, and activation of downstream signaling pathways. Concordantly, cell proliferation, migration, adhesion, and invasion were reduced. Furthermore, when GEF-H1 knockout (KO) cells were orthotopically implanted into the mammary fat pads of BALB/c mice, a significant decrease was observed in both tumor formation and lung metastasis compared to control breast cancer cells. These results suggest that GEF-H1/RhoA activation mediates cytoskeletal remodeling and signaling pathways critical for breast cancer cell proliferation, migration, and invasion. In vivo assays and human biopsy studies further support GEF-H1 as a potential biomarker of breast tumor progression
Palabras clave: GEF-H1 , RhoA , BREAST CANCER , METASTASIS , CYROSKELETON REGULATION
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/261332
URL: https://linkinghub.elsevier.com/retrieve/pii/S0925443925001619
DOI: http://dx.doi.org/10.1016/j.bbadis.2025.167816
Colecciones
Articulos(INIBIBB)
Articulos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
Fernández Chávez, Lucía; Schweitzer, Karen; Alonso, Exequiel Gonzalo; Ferronato, María Julia; Fermento, María Eugenia; et al.; GEF-H1 drives breast cancer cells to tumor progression; Elsevier Science; Biochimica et Biophysica Acta - Molecular Basis of Disease; 1871; 5; 26-3-2025; 1-16
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