Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

Deng, Ruyuan; Mo, Fengbo; Chang, Bowen; Zhang, Qi; Hui, Ran; Yang, Shuai; Zhu, Zhiqiang; Hu, Lei; Su, Qing

doi:10.18632/oncotarget.22185

Cited by 39 publications

(33 citation statements)

References 30 publications

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“…The RAGE-ligand signaling axis may promote the migration, invasion, and metastasis of a variety of cancers 5,14,44 . For example, the binding of RAGE and S100A8/A9 promotes the migration and invasion of human breast cancer cells 8 , and glucose-derived AGEs promotes the invasion and metastasis of gastric cancer through the activation of RAGE/ERK/Sp1/MMP2 pathway 45 . Moreover, expression of RAGE itself is also closely associated with the invasiveness and metastatic activities of gastric cancer 6 .…”

Section: Discussionmentioning

confidence: 99%

RAGE acts as an oncogenic role and promotes the metastasis of human lung cancer

Chen

Chang

et al. 2020

Cell Death Dis

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RAGE (receptor for advanced glycation end-product) is thought to be associated with metastasis and poor prognosis of various types of cancer. However, RAGE is constitutively expressed in the normal lung and down-regulated in cancerous lung, while the opposite evidence shows that RAGE-mediated signaling contributes to the tumorigenesis of lung cancer. Therefore, the role of RAGE in lung cancer progression is still unclear to be further investigated. In this study, RAGE-overexpressed stable clones of human lung cancer A549 cells and two local lung adenocarcinoma cell lines CL1-0 and CL1-5 were utilized to verify the effect of RAGE on lung cancer cells while the in vivo xenograft animal model was further performed to evaluate the role of RAGE in the progression of lung cancer. The growth of A549 cells was inhibited by RAGE overexpression. p53-dependent p21 CIP1 expression contributed to RAGE-induced growth inhibition by suppressing CDK2 kinase activity and retinoblastoma protein (RB) phosphorylation in vitro. On the other hand, RAGE overexpression promoted migration, invasion, and mesenchymal features of lung adenocarcinoma cells through ERK signaling. Furthermore, an in vivo xenograft experiment indicated that RAGE promoted the metastasis of lung cancer cells with p21 CIP1 up-regulation, ERK activation, and the changes of EMT markers. Regarding to the involvement of tumor-associated macrophage (TAM) in the microenvironment, we monitored the expressions of TAM markers including CD68 and CD163 as well as angiogenesis marker CD31 in xenograft slice. The data showed that RAGE might induce the accumulation of TAM in lung cancer cells and further accelerate the in vivo tumor growth. In summary, our study provides evidence indicating the distinct in vitro and in vivo effects of RAGE and related mechanisms on tumor growth and metastasis, which shed light on the oncogenic role of RAGE in lung cancer.

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Section: Discussionmentioning

confidence: 99%

RAGE acts as an oncogenic role and promotes the metastasis of human lung cancer

Chen

Chang

et al. 2020

Cell Death Dis

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“…[26][27][28] It can bind to specific sites on the promoter of vascular endothelial growth factor (VEGF) or VEGF receptor, which further promotes the progress of tumors. 29 SP1-regulated tumor-related genes are involved in a variety of cell functions, including cell cycle (Cyclin D1, TGF-α, E2F1), 30,31 apoptosis (Bax, Bcl2), 32,33 tumor metastasis (TGF-β, MMP2) 34 and angiogenesis (VEGF). 35 According to our results, Syncytin 1 may be one of the targets of SP1 in regulating the function of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

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“…MMPs family is known to cause chronic kidney disease, and kidney fibrosis present a failed wound healing in progressive chronic kidney disease (Klein, 2004). MMP-2 and MMP-9 are known to encourage cancer cell growth, including the metastasis of cancer cells (Deng, 2017) and has been shown to be profibrotic by induction of renal tubular cell epithelial-mesenchymal transition (Zhu, 2012). In the clinical studies demonstrated that serum MMP-2 and MMP-9 were higher levels in patients with type II Diabetes Mellitus (Signorelli, 2005;Derosa, 2007;Kostov, 2020).…”

Section: Discussionmentioning

confidence: 99%

The regulatory effects of resveratrol on the expression of renal MMP-2 and MMP-9 in the rat models of diabetes.

Bozkurt

Pektaş

2020

Anatolian Journal of Botany

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Hyperglycemia caused by diabetes mellitus, in sensitive tissues such as the kidney, can cause dysfunction by damaging the blood vessels. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, play a significant role in the degradation of proteins and angiogenesis; while epidermal growth factor receptor (EGFR) is involved in the recovery of damaged tissues. Herein, we investigated the relationship between MMP-2 and MMP-9 / EGFR in the kidney tissues of streptozotocin-induced Wistar male rats. We also examined the effects of resveratrol known as a strong tissue-protective on these changes. Diabetes was induced by streptozotocin (55 mg/kg) and trans-resveratrol (20 mg/kg/day intraperitoneal) was used for treatment. Rats were divided into 4 groups as control, resveratrol (Res), diabetes (Diab) and diabetes plus resveratrol (Diab+Res). Superoxide dismutase (SOD) and catalase (CAT) levels were significantly decreased in the kidneys in the diabetic group, whereas nitrite / nitrate, urea, creatine kinase (CK) and uric acid concentrations increased. MMP-2, MMP-9, calcium-binding protein B (S100B) and platelet-derived growth factor (PDGF) concentrations of kidney were increased although reduced EGFR in the diabetes group. Resveratrol supplementation markedly restored all these structures. Diabetes activates MMP related inflammation and oxidative stress by suppressing antioxidant enzymes in the kidney tissues. Resveratrol has partly modulatory effects on diabetes-induced changes.

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Glucose-derived AGEs enhance human gastric cancer metastasis through RAGE/ERK/Sp1/MMP2 cascade

Cited by 39 publications

References 30 publications

RAGE acts as an oncogenic role and promotes the metastasis of human lung cancer

RAGE acts as an oncogenic role and promotes the metastasis of human lung cancer

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

The regulatory effects of resveratrol on the expression of renal MMP-2 and MMP-9 in the rat models of diabetes.

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