Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells

Chappell, William H.; Abrams, Stephen L.; Lertpiriyapong, Kvin; Fitzgerald, Timothy L.; Martelli, Alberto M.; Cocco, Lucio; Rakus, Dariusz; Gizak, Agnieszka; Terrian, David M.; Steelman, Linda S.; McCubrey, James A.

doi:10.1016/j.jbior.2015.10.001

Cited by 33 publications

(25 citation statements)

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“…adrenal) or tissues [40–43]. And on another hand, the androgen/AR pathway is widely regulated, and can be activated vicariously [44, 45]. Considering the variable hormone conditions and AR regulations in particular tissues, the strategy to decrease the androgen in tumor microenvironment or to inhibit its binding to AR may be promising ways in treatment of such male bias cancers.…”

Section: Discussionmentioning

confidence: 99%

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

et al. 2016

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Hepatocellular carcinoma (HCC) is one of the most common and malignant cancers. The HCC incidence gets a strong sexual dimorphism as men are the major sufferers in this disaster. Although several studies have uncovered the presentative correlation between the axis of androgen/androgen receptor (AR) and HCC incidence, the mechanism is still largely unknown. Cancer stem cells (CSCs) are a small subgroup of cancer cells contributing to multiple tumors malignant behaviors, which play an important role in oncogenesis of various cancers including HCC. However, whether androgen/AR axis involves in regulation of HCC cells stemness remains unclear. Our previous study had identified that the pluripotency factor Nanog is not only a stemness biomarker, but also a potent regulator of CSCs in HCC. In this study, we revealed androgen/AR axis can promote HCC cells stemness by transcriptional activation of Nanog expression through directly binding to its promoter. In HCC tissues, we found that AR expression was abnormal high and got correlation with Nanog. Then, by labeling cellular endogenous Nanog with green fluorescent protein (GFP) through CRISPR/Cas9 system, it verified the co-localization of AR and Nanog in HCC cells. With in vitro experiments, we demonstrated the axis can promote HCC cells stemness, which effect is in a Nanog-dependent manner and through activating its transcription. And the xenografted tumor experiments confirmed the axis effect on tumorigenesis facilitation in vivo. Above all, we revealed a new sight of androgen/AR axis roles in HCC and provided a potential way for suppressing the axis in HCC therapy.

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Section: Discussionmentioning

confidence: 99%

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

et al. 2016

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“…EGFR knockdown phenocopied the effects of miR-3622b overexpression in PCa cell line, lending support to our hypothesis. Targeting the EGFR axis is a potential therapeutic strategy in prostate cancer [42, 43]. The combination of EGFR inhibitor gefitinib and radiation has been reported to have promising activity against prostate cancer [43].…”

Section: Discussionmentioning

confidence: 99%

Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21 regulates Epidermal Growth Factor Receptor in prostate cancer

et al. 2016

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Genomic loss of chromosome (chr) 8p21 region, containing prostate-specific NKX3.1 gene, is a frequent alteration of the prostate cancer (PCa) oncogenome. We propose a novel, paradigm shifting hypothesis that this frequently deleted locus is also associated with a cluster of microRNA genes- miR-3622a/b- that are lost in PCa and play an important mechanistic role in progression and metastasis. In this study, we demonstrate the role of miR-3622b in prostate cancer. Expression analyses in a cohort of PCa clinical specimens and cell lines show that miR-3622b expression is frequently lost in prostate cancer. Low miR-3622b expression was found to be associated with tumor progression and poor biochemical recurrence-free survival. Further, our analyses suggest that miR-3622b expression is a promising prostate cancer diagnostic biomarker that exhibits 100% specificity and 66% sensitivity. Restoration of miR-3622b expression in PCa cell lines led to reduced cellular viability, proliferation, invasiveness, migration and increased apoptosis. miR-3622b overexpression in vivo induced regression of established prostate tumor xenografts pointing to its therapeutic potential. Further, we found that miR-3622b directly represses Epidermal Growth Factor Receptor (EGFR). In conclusion, our study suggests that miR-3622b plays a tumor suppressive role and is frequently downregulated in prostate cancer, leading to EGFR upregulation. Importantly, miR-3622b has associated diagnostic, prognostic and therapeutic potential. Considering the association of chr8p21 loss with poor prognosis, our findings are highly significant and support a novel concept that associates a long standing observation of frequent loss of a chromosomal region with a novel miRNA in prostate cancer.

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“…Activation of MEKK-3 causes the phosphorylation of inhibitor of κB kinase (IKK), which subsequently phosphorylates the inhibitor of κB (IκB), leading to ubiquitination and degradation of IκB. NF-κB is thus released and then rapidly enters the nucleus to trigger transcription of multiple target genes, including cytokines, chemokines, matrix metalloproteinases (MMPs), a disintegrin and metalloprotease with thrombospondin motifs (ADAMTSs), and pro-survival genes [41,42]. Interestingly, NF-κB is also able to stimulate TNF-α production [21], thereby providing a positive feedback loop between both factors to further amplify the biological effects of TNF-α.…”

Section: Tnfr1-dependent Signaling Pathwaysmentioning

confidence: 99%

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

Wang¹,

Yu²,

Yan³

et al. 2017

ABBS

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Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to low back pain (LBP), which is a highly prevalent, costly, and crippling condition worldwide. Current treatments for IDD are limited to treat the symptoms and do not target the pathophysiology. Tumor necrosis factor-α (TNF-α) is one of the most potent pro-inflammatory cytokines and signals through its receptors TNFR1 and TNFR2. TNF-α is highly expressed in degenerative IVD tissues, and it is deeply involved in multiple pathological processes of disc degeneration, including matrix destruction, inflammatory responses, apoptosis, autophagy, and cell proliferation. Importantly, anti-TNF-α therapy has shown promise for mitigating disc degeneration and relieving LBP. In this review, following a brief description of TNF-α signal transduction, we mainly focus on the expression pattern and roles of TNF-α in IDD, and summarize the emerging progress regarding its inhibition as a promising biological therapeutic approach to disc degeneration and associated LBP. A better understanding will help to develop novel TNF-α-centered therapeutic interventions for degenerative disc disease.

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Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells

Cited by 33 publications

References 234 publications

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21 regulates Epidermal Growth Factor Receptor in prostate cancer

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

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Novel roles of androgen receptor, epidermal growth factor receptor, TP53, regulatory RNAs, NF-kappa-B, chromosomal translocations, neutrophil associated gelatinase, and matrix metalloproteinase-9 in prostate cancer and prostate cancer stem cells

Cited by 33 publications

References 234 publications

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

Androgen/androgen receptor axis maintains and promotes cancer cell stemness through direct activation of Nanog transcription in hepatocellular carcinoma

Novel tumor suppressor microRNA at frequently deleted chromosomal region 8p21 regulates Epidermal Growth Factor Receptor in prostate cancer

Tumor necrosis factor-&alpha;: a key contributor to intervertebral disc degeneration

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Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration