Résumé
[EN] 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 El and repression of transforming growth factor (TGF)-beta 2 genes. We also show that high levels ofJUNB switch the response of TGF-beta 2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-beta 2 production by promoting TGF-beta 2 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-beta 2 expression, which might be exploited for cancer prognosis and therapy.
This work was supported by:Fondo de Investigacion Sanitaria, ISCIII, grant number PI20-194, co-funded by ERDF/ESF, "Investing in your future".Generalitat Valenciana grant BEFPI/2013/060 for BPB.Generalitat Valenciana grant APOST 2016/001 for BPB.FEBS Short-Term Fellowship 2014 for BPB.Ministerio de Educacion, Cultura y Deporte grant FPU13/02755 for JMPS.Asociacion Espanola contra el cancer, AECC predoctoral grant for AMF.Part of the equipment employed in this work has been funded by Generalitat Valenciana and co-financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014-2020).
Pérez-Benavente, B.; Fathinajafabadi, A.; De La Fuente, L.; Gandía, C.; Martínez-Férriz, A.; Pardo-Sánchez, JM.; Milian-Medina, L... (2022). New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-B2. Genome Biology. 23(1):1-35. https://doi.org/10.1186/s13059-022-02800-0