Signal Transducers (STATs) 1 and 3 and Activator Protein 1 (AP-1) are transcription factors involved in the development of malignancy in colorectal carcinoma (CRC).
However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies.
This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention.
The main purpose of this review is the analysis of the expression patterns of AP-1 transcription factors in order to gain insight into the histophysiology of lymphoid tissues and the pathology of lymphoid malignancies.
Recent studies have suggested that JDP2 may function as a tumor suppressor through its suppressive action against the AP-1 complex, which is known to drive oncogenic signals in several human malignancies.
Previous study showed that repressor activator protein 1 regulates the transcriptional activity of nuclear factor-κB, and it was highly expressed in breast cancer tissues; however, the clinical significance of repressor activator protein 1 expression in cancer remains to be elucidated.
Thus, inflammatory cytokine TNF-α mediates genome-wide redistribution of the cREL/p63/p73, and AP-1 interactome, to diminish TAp73 tumor suppressor function and reciprocally activate NF-κB and AP-1 gene programs implicated in malignancy.
This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer.
Through interrogation of Cancer Genome Atlas data, we demonstrated that activation of the β1-integrin/FAK/cortactin/JNK1 signaling axis and associated differential regulation of activator protein 1 transcription factor target genes are plausible consequences of elevated cortactin protein levels.
Our results suggest that the AP-1/miR-101 feedback loop may prevent the excessive activation of metastatic signals imposed by ERK2/AP-1 and highlight the biological significance of miR-101 downregulation in cancer metastasis.
The effect of Tpl2 inhibition in cancer cells or endothelial cells was associated with inactivation of CCAAT/enhancer binding protein B, nuclear factor kappa-light-chain-enhancer of activated B cell and activator protein-1 and suppression of vascular endothelial growth factor.
The molecular mechanism(s) by which chronic inflammation drives cancer initiation and promotion include increased production of pro-inflammatory mediators, such as cytokines, chemokines, reactive oxygen intermediates, increased expression of oncogenes, COX-2 (cyclo-oxygenase-2), 5-LOX (5-lipoxygenase) and MMPs (matrix metalloproteinases), and pro-inflammatory transcription factors such as NF-κB (nuclear factor κB), STAT3 (signal transducer and activator of transcription 3), AP-1 (activator protein 1) and HIF-1α (hypoxia-inducible factor 1α) that mediate tumour cell proliferation, transformation, metastasis, survival, invasion, angiogenesis, chemoresistance and radioresistance.
Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC.
Suppressor of activator protein-1, regulated by interferon (SARI), is a recently identified tumor suppressor gene whose expression has been reported to be suppressed in several malignant neoplasms.
NF-κB and AP-1 provide mechanistic links between inflammation and cancer, and moreover regulate tumor angiogenesis and invasiveness, indicating that signaling pathways that mediate their activation provide attractive targets for new chemotherapeutic approaches.
These findings suggest that chloramphenicol-induced PI-3K/Akt, JNK phosphorylation, and activator protein 1 activation might function as a novel mitochondrial stress signal that result in an increase of MMP-13 expression and MMP-13-associated cancer cell invasion.
Because of the important role of the activator protein-1 (AP-1) transcription factor in cancer cells, we examined possible effects of HINT1 on AP-1 transcription factor activity in SW480 cells transfected with an AP-1-luciferase reporter.
The activator protein 1 (AP-1) and MAPK signaling pathways are believed to play an important role in cancer chemoprevention and chemotherapy due to their involvement in tumor cell growth, proliferation, apoptosis and survival.
Insofar as oxidative events regulate AP-1 and NF-kappaB transactivation, these oxidative events can be important molecular targets for cancer prevention.