New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-ß2.

BACKGROUND: JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unc...

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Detalles Bibliográficos
Autores: Perez-Benavente, Beatriz, Fathinajafabadi, Alihamze, de la Fuente, Lorena, Gandia, Carolina, Martinez-Ferriz, Arantxa, Pardo-Sanchez, Jose Miguel, Milian, Lara, Conesa, Ana, Romero, Octavio A, Carretero, Julian, Matthiesen, Rune, Jariel-Encontre, Isabelle, Piechaczyk, Marc, Farras, Rosa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p17057
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/17057
Access Level:acceso abierto
Palabra clave:AP-1/JUNB
Cancer progression
Cell cycle
ChIP-seq
Epithelial to mesenchymal transition
Transcriptome
Descripción
Sumario:BACKGROUND: JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear. RESULTS: Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-ß2 genes. We also show that high levels of JUNB switch the response of TGF-ß2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-ß2 production by promoting TGF-ß2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients. CONCLUSIONS: Our results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-ß2 expression, which might be exploited for cancer prognosis and therapy.

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