EPO gene expression promotes proliferation, migration and invasion via the p38MAPK/AP-1/MMP-9 pathway by p21WAF1 expression in vascular smooth muscle cells

Park, Sung Lyea; Won, Se Yeon; Song, Junhui; Kambe, Taiho; Nagao, Masaya; Kim, Wun-Jae; Moon, Sung‐Kwon

doi:10.1016/j.cellsig.2014.12.001

Cited by 26 publications

(22 citation statements)

References 29 publications

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“…We propose that EPO induces an increase of vimentin and Snail2 expression through a NFκB‐dependent pathway. Supporting our proposal, it has been demonstrated that EPO gene expression induces migration and invasion through MMP‐9 expression and NFκB activation in vascular smooth muscle cells and bladder cancer cells [Park et al, , ]. Our findings support our proposal that EPO induces an EMT process in MCF10A cells.…”

Section: Discussionsupporting

confidence: 91%

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Erythropoietin Induces an Epithelial to Mesenchymal Transition-Like Process in Mammary Epithelial Cells MCF10A

Ordoñez-Moreno

Rodriguez‐Monterrosas

Cortés‐Reynosa

et al. 2017

J. Cell. Biochem.

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Anemia is associated with chemotherapy treatment in cancer patients. Erythropoietin (EPO) has been used to treat anemia of cancer patients, because it stimulates erythropoiesis. However, treatment of breast cancer patients with EPO has been associated with poor prognosis and decrease of survival. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to a mesenchymal state. It has been implicated in tumor progression, because epithelial cells acquire the capacity to execute the multiple steps of invasion/metastasis process. However, the role of EPO on EMT process in human mammary epithelial cells has not been studied. In the present study, we demonstrate that EPO promotes a decrease of E-cadherin expression, an increase of N-cadherin, vimentin, and Snail2 expression, activation of FAK and Src kinases and an increase of MMP-2 and MMP-9 secretions. Moreover, EPO induces an increase of NFκB DNA binding activity, an increase of binding of p50 and p65 NFκB subunits to Snail1 promoter, migration, and invasion in mammary non-tumorigenic epithelial cells MCF10A. In summary, these findings demonstrate, for the first time, that EPO induces an EMT-like process in mammary non-tumorigenic epithelial cells. J. Cell. Biochem. 118: 2983-2992, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 91%

“…Comparisons were made to unstimulated cells. Ã P < 0.05. cells [Park et al, 2014[Park et al, , 2015. Our findings support our proposal that EPO induces an EMT process in MCF10A cells.…”

Section: Discussionsupporting

confidence: 90%

Erythropoietin Induces an Epithelial to Mesenchymal Transition-Like Process in Mammary Epithelial Cells MCF10A

Ordoñez-Moreno

Rodriguez‐Monterrosas

Cortés‐Reynosa

et al. 2017

J. Cell. Biochem.

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“…G 1 - to S-phase cell cycle progression has been implicated in the formation of vascular lesions in vascular disease [9]. To investigate the regulation of cell cycle events in NBL1 inhibition, we examined the expression of G 1 - to S-phase cell cycle associated proteins including cyclin D1, cyclin E, CDK2, CDK4 and CDK6 analysing by western blotting.…”

Section: Resultsmentioning

confidence: 99%

Inhibitory effect of NBL1 on PDGF-BB-induced human PASMC proliferation through blockade of PDGFβ-p38MAPK pathway

et al. 2016

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Pulmonary artery remodelling is a key feature in the pathological progress of pulmonary arterial hypertension (PAH). Moreover, excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) plays a critical role in the pathogenesis of pulmonary artery remodelling. Neuroblastoma suppressor of tumorigenicity 1 (NBL1) has been previously shown to induce growth inhibition in tumour cells. However, the effect of NBL1 in the regulation of human PASMC proliferation remains unclear. In cultured human PASMCs, we observed a dose-dependent inhibitory effect of NBL1 on platelet derived growth factor (PDGF)-BB-induced cell growth, DNA synthesis and proliferating cell nuclear antigen (PCNA) expression, as measured by MTS assay, 5-ethynil-2-deoxyuridine (EdU) analysis and western blots respectively. We also detected the expression and activities of cell-cycle positive regulators (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and negative regulators (p21 and p27) in human PASMCs by western blots and co-immuoprecipitation (IP). Our results show that NBL1-induced growth suppression is associated with the decreased activity of cyclin D1–CDK4 and the decreased phosphorylation of p27 in PDGF-BB-treated human PASMCs. By western blots using the phosphor-specific antibodies, we further demonstrated that NBL1 induced growth suppression is mediated by blockade of the up-stream PDGF-receptor β (PDGFRβ)-p38 mitogen-activated protein kinase (MAPK). In conclusion, our results suggest that NBL1 could inhibit PDGF-BB-induced human PASMC proliferation, and the underlying mechanism is associated with the decreased cyclin D1–CDK4 activity and up-regulated p27 by decreasing the phosphorylation of p27 via blockade of PDGFRβ-p38MAPK signal cascade. Our findings may provide a potential therapeutic target for PAH.

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“…Glycogen Synthase Kinase-3α/β (GSK3α/β) is one of the major downstream targets of Akt involved in migration and proliferation of VSMCs (Shin et al, 2003;Zhu et al, 2015). In addition, cyclin D1 and Matrix Metalloproteinase 9 (MMP9) have been shown to regulate cell cycle and cell migration respectively, and play crucial roles in the development of vascular lesion (Park et al, 2015;Shin et al, 2003). Understanding the link between WISP1 and Akt signaling may provide novel insight into mechanisms underlying VSMC proliferation and migration.…”

Section: Introductionmentioning

confidence: 99%

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

Líu

et al. 2016

European Journal of Pharmacology

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EPO gene expression promotes proliferation, migration and invasion via the p38MAPK/AP-1/MMP-9 pathway by p21WAF1 expression in vascular smooth muscle cells

Cited by 26 publications

References 29 publications

Erythropoietin Induces an Epithelial to Mesenchymal Transition-Like Process in Mammary Epithelial Cells MCF10A

Erythropoietin Induces an Epithelial to Mesenchymal Transition-Like Process in Mammary Epithelial Cells MCF10A

Inhibitory effect of NBL1 on PDGF-BB-induced human PASMC proliferation through blockade of PDGFβ-p38MAPK pathway

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

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