New roles for AP-1/JUNB in cell cycle control and tumorigenic cell invasion via regulation of cyclin E1 and TGF-β2

Abstract

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)-β2 genes. We also show that high levels of JUNB switch the response of TGF-β2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-β2 production by promoting TGF-β2 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-β2 expression, which might be exploited for cancer prognosis and therapy.

The CD4 T cell epigenetic JUNB+ state is associated with proliferation and exhaustion

“…Further evidence suggests that ZNF331 can act upstream, including the presence of ChIP-seq peaks at both 5’ and 3’ of JUNB (Figure 6d). ZNF331 OE also induces G2 cell cycle arrest in cancer 39 ; assuming JUNB is related to cell cycle control, as suggested by our cluster, and previously shown 40 , then the phenotype of ZNF331 OE is also consistent with being upstream. However, we expect the regulation of JUNB to be more complex than being run by a single gene.…”

Benzo[a]pyrene Exposure Reduces Cell-Type Diversity and Stimulates Sex-Biased Damage Pathways in End Organs of Lupus-Prone Mice

“…These vasculature genes included Efnb2 , a member of the ephrin family and a pro-angiogenic factor whose overexpression predicts the poor prognosis of solid tumors [ 43 , 44 , 45 ], and Id1 , a helix–loop–helix transcription factor that regulates tumor angiogenesis [ 46 ] ( Figure 4 E,F). BaP upregulated the expression levels of these pro-angiogenic and pro-tumorigenic factors [ 47 , 48 , 49 ] in male MRL lungs more than in their female counterparts ( Figure 4 F). Immunofluorescence staining also showed that there was an increase in the number of EFNB2-positve cells in the lungs of BaP-treated MRL mice, an effect more substantial in males than females ( Figure 4 G,H).…”

Chromatin accessibility uncovers KRAS-driven FOSL2 promoting pancreatic ductal adenocarcinoma progression through up-regulation of CCL28

“…Furthermore, we did not examine whether other AP-1 members showed expression correlation with CCL28 and KRAS, or whether they regulated tumour growth. However, previous reports have shown that FOS transcription can mediate YAP/TAZ to promote cell proliferation [ 63 ], JUNB can promote cell cycle progression by inducing cyclin E1 and repressing transforming growth factor (TGF)-β2 genes [ 64 ], and CRTC1 can associate with c-Jun and c-Fos to activate transcription and promote cellular proliferation [ 65 ]. To date, no studies have explored the association between other AP-1 families and CCL28.…”