High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway

Zhang, Jingliang; Shao, Shuai; Han, Donghui; Xu, Yiming; Jiao, Dian; Wu, Jieheng; Fa, Yang; Ge, Yufeng; Shi, Shengjia; Yu, Li; Wen, Weihong; Qin, Weijun

doi:10.3892/ijo.2018.4420

Cited by 50 publications

(78 citation statements)

References 49 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on previously reported results, the activation of the NF-κB signaling pathway is of primary importance for the cellular action of the RAGE receptor. 22,23,[35][36][37] We used an NF-κB reporter gene assay to confirm the functionality of this system by transfection of a pMEKK positive control, 38 and we demonstrated an increase in luciferase activity by a factor 2.38 after 45 minutes (Fig. 2C, left panel).…”

Section: Characterization Of the Rage Pathway And Its Functionality Imentioning

confidence: 85%

Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells

Gross

Belville

Lavergne

et al. 2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE.We used a human corneal epithelial cell (HCE) line to determine the involvement of the advanced glycation end products (AGEs) / receptor for AGEs (RAGE) couple in corneal epithelium wound healing. METHODS.After wounding, HCE cells were exposed to two major RAGE ligands (HMGB1 and AGEs), and wound healing was evaluated using the in vitro scratch assay. Following wound healing, the HCE cells were used to study the influence of the RAGE ligands on HCE proliferation, invasion, and migration. Activation of the nuclear factor (NF)-κB signaling pathway by the AGEs/RAGE couple was tested using a luciferase reporter assay. Functional transcriptional regulation by this pathway was confirmed by quantification of expression of the connexin 43 target gene. For each experiment, specific RAGE involvement was confirmed by small interfering RNA treatments. RESULTS.AGEs treatment at a dose of 100 μg/mL significantly improved the wound healing process in a RAGE-dependent manner by promoting cell migration, whereas HMGB1 had no effect. No significant influence of the AGEs/RAGE couple was observed on cell proliferation and invasion. However, this treatment induced an early activation of the NF-κB pathway and positively regulated the expression of the target gene, connexin 43, at both the mRNA and protein levels. CONCLUSIONS.Our results demonstrate that the RAGE pathway is activated by AGEs treatment and is involved in the promotion of corneal epithelial wound healing. This positive action is observed only during the early stages of wound healing, as illustrated by the quick activation of the NF-κB pathway and induction of connexin 43 expression.

show abstract

Section: Characterization Of the Rage Pathway And Its Functionality Imentioning

confidence: 85%

Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells

Gross

Belville

Lavergne

et al. 2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The mean serum HMGB1 level was 4.64 ng/mL in patients with malignant breast cancer, which was remarkably higher than in patients with benign breast cancer (1.32 ng/mL) or in healthy subjects (1.36 ng/mL) [75]. HMGB1 (2 µg/mL) induces EMT of colorectal and prostate cancer cells via the RAGE/NF-κB pathway [76,77]. IL-10 is a potent anti-inflammatory cytokine that suppresses T cell/macrophage cytokine synthesis and blocks their antigen-presenting capacity [78].…”

Section: Emt Inducers From Chronic Inflammatory Tumor Microenvironmentsmentioning

confidence: 83%

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

Lee

2019

Cancers

View full text Add to dashboard Cite

Epithelial mesenchymal transition (EMT) is a key process in the progression of malignant cancer. Therefore, blocking the EMT can be a critical fast track for the development of anticancer drugs. In this paper, we update recent research output of EMT and we explore suppression of EMT by natural anti-inflammatory compounds and pro-resolving lipids.A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the m ajor signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2) belongs to the runt-related transcription factor family [19]. Runx2 plays a key role in EMT of hepatocellular carcinoma (HCC) [20]. GATA transcription factors are also implicated in the EMT of cancer cells [21].A typical signaling pathway of EMT is the transforming growth factor-β1 (TGF-β1) pathway. TGF-β1 induces EMT via SMAD-dependent or non-SMAD signaling pathway [7]. Growth factors including FGF, HGF, IGF1, EGF, and PDGF via receptor tyrosine kinase can induce EMT via signaling pathway of PI3K-AKT and ERK MAPK [8][9][10][11]. Wnt signaling, hedgehog signaling, Notch signaling, hypoxia, and inflammatory tumor microenvironment also involves in EMT [5]. Recently, it has been shown that hippo signaling is also involved in EMT [12]. YAP and TAZ can enhance EMT through upregulation of EMT transcription factors such as forkhead box C2 (FOXC2), snail family zinc finger 1/2 (SNAIL1, SLUG), twist-related protein 1 (TWIST1), and ZEB1 [12-15]. Transcription Factors Involved in EMTNovel players are newly recognized as regulatory transcription factor in the EMT. Brachyury, the T-box transcription factor, is a novel transcription factor implicated in the EMT of cancer cells [16]. Brachyury is known as the target gene of WNT, one of the major signaling pathways of EMT [17]. Foxq1, one of forkhead transcription factor, has also regarded as a novel transcription factor mediating the EMT of gastric cancer [6,18]. Runt-related transcription factor 2 (Runx2...

show abstract

“…We performed IHC to identify HMGB1 expression patterns in patient tissue and explore the clinical signi cance of HMGB1 in PCa. Several researchers have reported that high HMGB1 expression was associated with pathological features, such as Gleason score, pathological stage, PSA level, and metastasis [18][19][20]. However, most of the previous studies did not analyze the expression pattern according to the stage and nuclear grade of PCa.…”

Section: Discussionmentioning

confidence: 99%

“…NF-κB signaling plays a pivotal role in cancer cell proliferation, progression, and metastasis in PCa cells [14]. An association between HMGB1 and the NF-κB signaling pathway has been widely evaluated in several solid cancers and in ammation, but rarely in PCa [15]. For this reason, we next investigated if HMGB1down-regulation could affect NF-κB signaling in prostate cancer cells using a human NF-κB proteome pro ler array.…”

Section: Suppression Of Hmgb1 Expression Inhibits the Nf-κb Pathway Imentioning

confidence: 99%

HMGB1/TNFR1/NF-κB Axis in Prostate cancer: Clinical and Biological Correlation

Jung

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background High mobility group box 1 protein (HMGB1) is known to be associated with progression, metastasis, and poor prognosis of several solid tumors, but the role of HMGB1 in prostate cancer (PCa) has remained unclear. Thus, we aimed to evaluate the clinical significance and the biological mechanism of HMGB1 in PCa. Methods To explore the clinical significance of HMGB1 in PCa, we performed IHC analyses using paraffin-embedded tissues from patients with low-, intermediate-, and high-risk PCa and from patients with BPH. Biological role and mechanism of HMGB1 in PCa were analyzed using cell viability, cell cycle, Western blot analyses, proteome profiler antibody array, and co-immunoprecipitation assay. Results We showed that increases in the expression of HMGB1 correlated with an increased risk of aggressive PCa, and high expression of HMGB1 was associated with poor biochemical recurrence-free survival in a Korean cohort. The inhibition of HMGB1 expression significantly reduced cell proliferation and increased cell cycle arrest in the sub-G0 phase. It also inhibited the invasive capacity of PCa cells in vitro. The above processes were mediated through the binding with TNFR1, leading to tumor progression by activation of the NF-κB signaling pathway. Conclusions We identified that HMGB1 is a critical factor in the development and progression of PCa by regulating the HMGB1/TNFR1/NF-κB signaling pathway. HMGB1/TNFR1 could serve as a novel therapeutic target for improving PCa therapy.

show abstract

High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway

Cited by 50 publications

References 49 publications

Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells

Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells

Reversal of Epithelial–Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids

HMGB1/TNFR1/NF-κB Axis in Prostate cancer: Clinical and Biological Correlation

Contact Info

Product

Resources

About