Cyr61 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by Raf-1/MEK/ERK/Elk-1/TWIST-1 signaling pathway

Hou, Chun‐Han; Lin, Feng; Hou, Sheng Mon; Liu, Ju-Fang

doi:10.1186/1476-4598-13-236

Cited by 111 publications

(95 citation statements)

References 55 publications

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“…It is possible that IGFBP10/CYR61/CCN1 can suppress hepatocarcinogenesis by inhibiting compensatory proliferation [34], although its role in tumor growth is not well established yet. At the same time, an increased level of CYR61/CCN1 as well as a decreased level of NOV/CCN3 possibly has relation to increased metastasis of glioma cells without IRE1 function [40], because CYR61/CCN1 is responsible for induction of the tumor epithelial-mesenchymal transition, invasion, and metastasis as well as inhibition of NOV levels promotes the invasive phenotype of metastatic cancer cells [35]. Furthermore, elevated levels of WISP1 and CYR61 in primary breast cancers associated with more advanced features [14].…”

Section: Fig 4 Effect Of Hypoxia On the Expression Of Insulinlike Gmentioning

confidence: 99%

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Minchenko¹,

Kharkova²,

Minchenko³

et al. 2015

Ukr.Biochem.J.

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Insulin-like growth factor binding proteins (IGFBPs ) contain insulin-like growth factor (IGF) binding domain and play an important role in the regulation of numerous metabolic and proliferative processes mainly through interaction with IGF1 and IGF2, their cell surface receptors as well as insulin receptor, alter the half-life of the IGFs, modifying their biological activity. It is well known that insulin-like growth factors and the signal transduction networks play important roles in tumorigenesis and metastasis as well as in metabolic diseases [1,2]. IGFBPs participate in endoplasmic reticulum stress, which is an important factor of tumor growth, insulin resistance, and obesity [3][4][5]. It is interesting to note that there is the cross talk between IGF and insulin receptor signaling pathways at the receptor level or at downstream signaling level. This cross talk significantly changed a variety of cancers as a result of insulin receptor isoform. A formation of hybrid receptor isoforms between receptors for IGF1 and insulin, which are sensitive to the stimulation of all three IGF axis ligands, as well as hybrid receptors of IGF1/insulin receptor with other tyrosine kinase potentiate the transformation of cells, tumorigenesis, and tumor neovascularization [6].The IGFBPs have different affinity for insulin-like growth factors. They bind and regulate the availability of both insulin-like growth factors and inhibit or stimulate the growth promoting effects of the IGFs through IGF/INS receptors and through other signaling pathways and regulate cell proliferation and survival as well as angiogenesis and cancer експериментальні роботи doi: http://dx

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Section: Fig 4 Effect Of Hypoxia On the Expression Of Insulinlike Gmentioning

confidence: 99%

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Minchenko¹,

Kharkova²,

Minchenko³

et al. 2015

Ukr.Biochem.J.

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“…Cyr61 is up regulated in many cancers, such as breast [19], esophagus [22], and colorectal cancers [23]. Several studies have reported that Cyr61 promotes the EMT and tumor metastasis [24,25].…”

Section: Introductionmentioning

confidence: 99%

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

Huang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. Methods: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. Results: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced “CRC cell” migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. Conclusions: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC.

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“…Previous studies have aimed to develop specific therapeutic approaches targeting metastatic progression, and to understand the mechanisms underlying metastasis (4,5). Cysteine-rich angiogenic inducer 61 has been reported to promote the epithelial to mesenchymal transition of osteosarcoma (6). In addition, Ezrin expression has been reported to be necessary for metastasis of osteosarcoma (7), and high expression levels of transforming growth factor-β (TGF-β) have been observed in osteosarcoma cell lines (8).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

Jia

Bai

et al. 2017

Molecular Medicine Reports

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Abstract. The present study aimed to understand the molecular mechanisms underlying osteosarcoma metastasis. Microarray dataset GSE49003 was downloaded from the Gene Expression Omnibus database and used for analysis. Raw expression data were preprocessed using the preprocessCore, impute and aggregate packages in R. Differentially expressed genes (DEGs) between metastatic and non-metastatic osteosarcoma cell lines were screened using the limma package following exclusion of DEGs with a higher significance in intra-groups compared with inter-groups using the genefilter package. Enrichment analysis was performed on DEGs using TargetMine, followed by identification of transcription factors (TFs) and microRNAs (miRNAs). Regulatory networks were constructed using Cytoscape software. A total of 248 upregulated and 208 downregulated genes were obtained. The upregulated genes were significantly enriched in the following pathways: Downregulation of transforming growth factor β (TGF-β) receptor signaling and TGF-β receptor signaling activates SMADs; these upregulated genes included protein phosphatase 1, regulatory subunit 15A, transforming growth factor, β receptor II and ubiquitin carboxyl-terminal hydrolase L5. In addition, some upregulated genes were enriched in lung cancer disease ontology, including epidermal growth factor receptor (EGFR), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1). Conversely, the downregulated genes were significantly enriched in extracellular matrix-associated pathways or functions, such as collagen, type XII, α 1; collagen, type I, α 1; collagen, type IV, α 1; and collagen, type V, α 1. In addition, some downregulated genes were significantly enriched in the TGF-β signaling pathway, including bone morphogenetic protein 4, inhibitor of DNA binding 3 and SMAD family member 6. A total of 10 TFs and 84 miRNAs (e.g. miR-21-5p) were deemed to be associated with DEGs. In conclusion, DEGs enriched in the downregulation of TGF-β receptor signaling, TGF-β receptor signaling activates SMADs and TGF-β signaling pathways, as well as the extracellular matrix may be implicated in the progression of osteosarcoma metastasis. Dysregulated EGFR, IGF2BP3, RUNX3 and SFRP1 may contribute to the metastasis of osteosarcoma to the lungs. In addition, screened TFs and miR-21-5p may be associated with metastasis via target genes.

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Cyr61 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by Raf-1/MEK/ERK/Elk-1/TWIST-1 signaling pathway

Cited by 111 publications

References 55 publications

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer

Molecular characterization of metastatic osteosarcoma: Differentially expressed genes, transcription factors and microRNAs

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