STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

Ko, Hyun Sun; Park, Byung Joon; Choi, Sae Kyung; Kang, Hee Kyung; Kim, Ah Young; Kim, Ho Shik; Park, In Yang; Shin, Jong Chul

doi:10.3349/ymj.2016.57.3.761

Cited by 28 publications

(23 citation statements)

References 24 publications

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“…The MAPK/ERK signaling pathway is a highly conserved intracellular pathway that plays vital roles in the transmission of signals to the cell nucleus; these signals then transcriptionally regulate genes that are involved in various cellular processes, including cell invasion and metastasis ( 4 – 6 ). The invasion and metastasis of tumor cells, and the related degradation of the extracellular matrix (ECM) are closely associated with the development of malignant tumors.…”

Section: Introductionmentioning

confidence: 99%

Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling

Wen

Liang

Pan

2017

International Journal of Molecular Medicine

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The overexpression of eyes absent (Eya) 2 has been found in several human cancers. However, its biological roles and clinical significance in human astrocytoma have not yet been explored. This study investigated the clinical significance and biological roles of Eya2 in human astrocytoma tissues and cell lines. Using immunohistochemistry, we found Eya2 overexpression in 33 out of 90 (36.7%) astrocytoma specimens. The rate of Eya2 overexpression was higher in grade III–IV (48.1%) than in grade I+II astrocytomas (21.1%). Transfection with an Eya2 expression plasmid was performed in A172 cells with a low endogenous expression of Eya2 and the knockdown of Eya2 was carried out in U251 cells with a high endogenous expression using siRNA. Eya2 overexpres-sion induced A172 cell proliferation and invasion, while the knockdown of Eya2 using siRNA decreased the proliferation and invasion of U251 cells. In addition, we found that transfection with the Eya2 expression plasmid facilitated cell cycle progression, and that the knockdown of Eya2 inhibited cell cycle progression, accompanied by a change in the expression of cell cycle-related proteins, including cyclin D1 and cyclin E. Eya2 also positively regulated extracellular signal-regulated kinase (ERK) activity and matrix metalloproteinase (MMP)9 expression. The blockade of ERK signaling using an inhibitor abolished the effects of Eya2 on A172 cell invasion and MMP9 production. In addition, we found that there was a positive correlation between Eya2 and Six1 in the astrocytoma cell lines. Immunoprecipitation revealed that Eya2 interacted with Six1 protein in the U251 cell line, which exhibited a high expression of both proteins. Eya2 failed to upregulate MMP expression in the A172 cells in which Six1 was silenced. On the whole, our data indicate that Eya2 may serve as a potential oncoprotein in human astrocytoma. Eya2 regulates astrocytoma cell proliferation and invasion, possibly through the regulation of ERK signaling.

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Section: Introductionmentioning

confidence: 99%

Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling

Wen

Liang

Pan

2017

International Journal of Molecular Medicine

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“…Our results also indicated that ERK1/2 and PI3K/AKT pathways result in phosphorylation of STAT3 and STAT5 in GBM. Other authors have implicated STAT3 and ERK signaling pathways in the invasion of HTR8/SVneo cells (an immortalized human trophoblast line) via induction of MMP-9 [ 36 ]. However, the scope of that study did not extend to the putative relationship between ERK1/2 + PI3K/AKT and STAT3 + STAT5.…”

Section: Discussionmentioning

confidence: 99%

EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism

et al. 2017

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Epidermal growth factor (EGF) and EGF receptor (EGFR) play prominent roles in the metastasis of glioblastoma (GBM). However, the molecular mechanisms for the function of EGF and EGFR in GBM metastasis have not been elucidated. Herein, we demonstrate that coactivation of EGF and EGFR drives tumor metastasis in a matrix metalloproteinase-9 (MMP-9)–dependent manner. Expression levels of EGF, EGFR, and MMP-9 were substantially upregulated in the GBM and edema zones of patients, compared with those of paired unaffected participants. Secretion of EGF and MMP-9 was reduced in the cerebrospinal fluid (CSF) after removing GBM for 2 weeks by operation. To the mechanism, MMP-9 was upregulated by activating EGF and EGFR via PI3K/AKT- and ERK1/2-dependent pathways. Moreover, signal transducer and activator of transcription (STAT) 3 and STAT5 mediated the activation of NF-κB by PI3K/AKT and ERK1/2 pathways. This resulted in transactivation of MMP-9 in GBM. Finally, MMP-9 induction facilitated abnormal proliferation, migration, and invasion of cells, which contributed to GBM metastasis.

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“…A number of reports have demonstrated that inhibiting the ERK/CREB pathway and regulating the expression of Bax, Bcl-2 and survivin may suppress the proliferation of cancer cells ( 17 , 20 – 22 ). In addition, inhibition of ERK/CREB signaling pathway may suppress the migration and invasion of human chorionic trophoblast cells and lung cancer cells by decreasing the expression and activation of MMP2 and MMP9 ( 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

CT45A1 siRNA silencing suppresses the proliferation, metastasis and invasion of lung cancer cells by downregulating the ERK/CREB signaling pathway

Tang

Sheng-jun

Guo

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to investigate the role of the cancer-testis antigen family 45 member A1 (CT45A1) in the proliferation, apoptosis, invasion and metastasis of lung cancer cells, and the associated molecular mechanisms. Western blotting determined that the expression of CT45A1 in normal lung cells was far lower than that observed in lung cancer cells. Following the transfection of CT45A1 small (or short) interfering (si)RNA and its negative control into A549 cells using Lipofectamine 2000, the CT45A1 protein and mRNA levels were determined further by western blotting and reverse transcription-polymerase chain reaction. Following CT45A1 siRNA transfection, the levels of CT45A1 in lung cancer cells were markedly reduced (P<0.01). Then, cell viability and apoptosis were investigated with a methyl thiazolyl tetrazolium assay and Annexin V-FITC/propidium iodide staining, respectively. Transwell assays were employed to evaluate the migration and invasion of A549 cells. When compared with the negative control, the viability, migration and invasion of lung cancer cells treated with CT45A1 siRNA were suppressed and apoptosis was promoted (all P<0.01). In addition, the levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), survivin, matrix metalloproteinase 2 (MMP2), MMP9, extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), cyclic AMP response element binding protein (CREB) and p-CREB were assessed by western blotting. Following CT45A1 silencing, the expressions of Bcl-2, survivin, MMP2, MMP9, p-ERK1/2 and p-CREB were downregulated and the expression of Bax was upregulated (all P<0.01). It was concluded that CT45A1 siRNA silencing suppressed the proliferation, metastasis and invasion of lung cancer cells by downregulating the ERK/CREB signalling pathway.

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STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

Cited by 28 publications

References 24 publications

Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling

Eya2 overexpression promotes the invasion of human astrocytoma through the regulation of ERK/MMP9 signaling

EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism

CT45A1 siRNA silencing suppresses the proliferation, metastasis and invasion of lung cancer cells by downregulating the ERK/CREB signaling pathway

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