New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-B2

Abstract

[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.