A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

Liu, Bingshan; Li, Guojun; Wang, Xiao; Liu, Yang

doi:10.3892/ol.2014.1839

Cited by 13 publications

(15 citation statements)

References 37 publications

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“…The results showed inhibition of PIM1 expression by PIM1 siRNA was accompanied with down‐regulation of Bcl‐2, survivin, and Bcl‐XL expressions and change in Bcl‐2 was the most significant. MT1‐MMP is a zinc‐dependent type‐I transmembrane metalloproteinase that plays pivotal roles in cellular migration and invasive processes in osteosarcoma . In this study, the decreased PIM1 expression by siRNA was also accompanied by down‐regulated expression of MT1‐MMP.…”

Section: Discussionmentioning

confidence: 61%

Clinical and biological significance of PIM1 kinase in osteosarcoma

Liao

Feng

Shen

et al. 2015

Journal Orthopaedic Research

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Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene serine/ threonine-protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down-regulation of anti-apoptotic protein Bcl-2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. ß

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Section: Discussionmentioning

confidence: 61%

Clinical and biological significance of PIM1 kinase in osteosarcoma

Liao

Feng

Shen

et al. 2015

Journal Orthopaedic Research

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“…Additionally, the Wnt/b-catenin signaling is correlated with MMP-1 and MMP-7 levels in other tumor cells. 34,35 We demonstrated that Wnt/b-catenin pathway was activated in glioma cells, but inactivated by GPNMB suppression, and the activity of MMPs in glioma cells was mediated by Wnt/bcatenin pathway.…”

Section: Discussionmentioning

confidence: 96%

Glycoprotein non-metastaticmelanoma protein B promotes glioma motility and angiogenesis through the Wnt/β-catenin signaling pathway

Bao

Wang

et al. 2016

Exp Biol Med (Maywood)

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Glioma is a common tumor with high mortality and poor overall survival. However, the regulatory mechanisms of glioma tumorigenesis and glioma cell motility are completely unknown. Here, we investigated the role of glycoprotein non-metastatic melanoma protein B in glioma. The expression of glycoprotein non-metastatic melanoma protein B is observed to be aberrantly regulated in glioma tissues and cells, and high levels of glycoprotein non-metastatic melanoma protein B present an inverse correlation with the survival of glioma patients. Compared with the control, glycoprotein non-metastatic melanoma protein B inhibition significantly retarded the proliferation and migration of human glioma cells. The tube formation ability of HBMECs induced by glioma cells was also remarkably reduced by glycoprotein non-metastatic melanoma protein B silencing. Increased levels of VEGF-C and TEM7 were down-regulated by the suppression of glycoprotein non-metastatic melanoma protein B in glioma cells. Additionally, the activity of MMP-2/3/9 was assessed in glioma cells using Western blotting and gelatin zymography assay; their activities were strongly decreased following the suppression of glycoprotein non-metastatic melanoma protein B. Further studies suggested that canonical Wnt/b-catenin pathway was activated, but was inactivated by glycoprotein non-metastatic melanoma protein B suppression in glioma cells.In conclusion, we demonstrate that glycoprotein non-metastatic melanoma protein B might be an inducer for glioma and could enhance matrix metalloproteinase activity through Wnt/b-catenin pathway to contribute to glioma tumorigenesis. This may represent a new understanding for malignant glioma.

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“…The associations between different signaling pathways and MMPs have been investigated in a number of cell culture systems (46–48). Using selective pharmaceutical inhibitors of EGFR downstream signaling pathway effectors, the present study revealed that MMP-1 expression was upregulated through the MAPK/ERK signaling pathway in SiHa cells treated with EGF and MβCD, and that the PI3-K/AKT, p38 MAPK and JNK/MAPK signaling pathways were not involved in this process.…”

Section: Discussionmentioning

confidence: 99%

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

Zhang

Wang

et al. 2016

Oncology Letters

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Matrix metalloproteinase-1 (MMP-1) has been identified as an important participant in tumor invasion, metastasis and angiogenesis. The purpose of the present study was to investigate the effects of epidermal growth factor receptor (EGFR) localization to lipid rafts on signaling pathways involved in the regulation of MMP-1 expression in SiHa cells, a cervical cancer cell line. EGFR activation by EGF specifically induced MMP-1 expression at both the messenger RNA and protein levels. Additionally, it was observed that EGFR localized to lipid rafts, and that the redistribution of EGFR induced by lipid raft disruption strengthened EGF-induced MMP-1 expression. MMP-1 induction was blocked by the mitogen-activated protein kinase (MAPK) kinase inhibitors PD98059 and U0126. Our results suggested that lipid rafts provide a platform to inhibit EGFR regulation of MMP-1 in SiHa cells through the MAPK/extracellular signal-regulated kinase signaling pathway.

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A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

Cited by 13 publications

References 37 publications

Clinical and biological significance of PIM1 kinase in osteosarcoma

Clinical and biological significance of PIM1 kinase in osteosarcoma

Glycoprotein non-metastaticmelanoma protein B promotes glioma motility and angiogenesis through the Wnt/β-catenin signaling pathway

Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway

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