c-Myc Overexpression Promotes Osteosarcoma Cell Invasion Via Activation of MEK-ERK Pathway

Hou, Gang; Wang, Yan; Bi, Wenzhi

doi:10.3727/096504012x13522227232237

Cited by 84 publications

(68 citation statements)

References 2 publications

(2 reference statements)

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“…Furthermore, it was reported that the MMP-2 and MMP-9 were indirectly upregulated by c-myc (Han et al, 2012). Our experiments showed that following the c-myc decrease, the expression of MMP-9 was downregulated in breast cancer cells infected by the Ad-COX-2-shRNA.…”

Section: Targeting Of Cox-2 Expression By Recombinant Adenovirusupporting

confidence: 52%

“…C-myc directly promotes cyclin D1 expression (Asara et al, 2013;Daksis et al, 1994), and cyclin D1 activation kinases regulate the phosphorylation of retinoblastoma protein (pRb) (Hochegger et al, 2008). Recent advances strongly support that C-myc plays multiple functions on cell proliferation, apoptosis and invasion (Han et al, 2012). Matrix metalloproteinases (MMPs), the zinc containing enzymes to degrade extracellular matrix components, play a crucial role in the invasion and metastasis of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Targeting of COX-2 Expression by Recombinant Adenovirus shRNA Attenuates the Malignant Biological Behavior of Breast Cancer Cells

Ma²,

Peng³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Targeting Of Cox-2 Expression By Recombinant Adenovirusupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Targeting of COX-2 Expression by Recombinant Adenovirus shRNA Attenuates the Malignant Biological Behavior of Breast Cancer Cells

Ma²,

Peng³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Notably, an orthotopic study in mice with phospho‐specific antibodies and kinase inhibitors revealed that only IGF‐IR/MEK pathway, but not IGF‐IR/AKT pathway, remain active in lung metastasis, suggesting that Ras/Raf/MEK/ERK signaling may play an important role in osteosarcoma lung metastasis (Yu et al., 2011). In addition, c‐Myc overexpression enhanced MG‐63 and SAOS‐2 osteosarcoma cells invasion through the activation of MEK‐ERK pathway whereas inhibited the activity of PI3K‐AKT pathway (Han et al., 2012). Further downstream in IGF‐I signaling is the Nuclear Receptor Coactivator 3 (NCOA3), which was reported to be overexpressed in osteosarcomas driving its progression (Geng et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

et al. 2016

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Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high‐throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho‐AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression also associated with lower overall survival but was not strong enough to be considered an independent variable. Interestingly, miR‐200c was overexpressed in lung metastases, implicating an inhibitory feed‐back loop to PI3K‐AKT. Moreover, transfection of miR200c‐mimic in U2‐OS cells reduced phospho‐AKT levels but increased cellular migration and proliferation. Notably, miR‐200c expression strongly correlated with miR‐141 and with the osteogenic inhibitor miR‐375, all implicated in epithelial to mesenchymal transition. These findings contrast epithelial tumors where reduced miR‐200c expression promotes metastasis. Indeed, we noted that osteosarcoma cells in the lung also expressed the epithelial marker CDH1, revealing a change in their mesenchymal phenotype. We propose that miR‐200c upregulation occurs late in osteosarcoma progression to provide cells with an epithelial phenotype that facilitates their integration in the metastatic lung niche. Thus, our findings identify phospho‐AKT in the primary tumor and miR‐200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.

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“…In recent years, developments in molecular biology have provided new insights into potential diagnostic and therapeutic biomarkers for osteosarcoma. Previous study demonstrated that prometastasis genes such as MYC and RAS facilitate osteosarcoma metastasis and metastasis‐resistant genes including nm23 , p16 and KiSS‐1 metastasis‐suppressor inhibited the metastasis process in osteosarcoma. Furthermore, microarray technology has been widely used for screening a series of metastasis‐related genes in osteosarcoma .…”

mentioning

confidence: 99%

A risk score model for the prediction of osteosarcoma metastasis

et al. 2019

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Osteosarcoma is the most common primary solid malignancy of the bone, and its high mortality usually correlates with early metastasis. In this study, we developed a risk score model to help predict metastasis at the time of diagnosis. We downloaded and mined four expression profile datasets associated with osteosarcoma metastasis from the Gene Expression Omnibus. After data normalization, we performed LASSO logistic regression analysis together with 10‐fold cross validation using the GSE21257 dataset. A combination of eight genes ( RAB 1 , CLEC 3B , FCGBP , RNASE 3 , MDL 1 , ALOX 5 AP , VMO 1 and ALPK 3 ) were identified as being associated with osteosarcoma metastasis. These genes were put into a gene risk score model, and the prediction efficiency of the model was then validated using three independent datasets ( GSE33383 , GSE66673 , and GSE49003 ) by plotting receiver operating characteristic curves. The expression levels of the eight genes in all datasets were shown as heatmaps, and gene ontology gene annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. These eight genes play a role in cancer‐related biological processes, such as apoptosis and biosynthetic processes. Our results may aid in elucidating the possible mechanisms of osteosarcoma metastasis, and may help to facilitate the individual management of patients with osteosarcoma after treatment.

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c-Myc Overexpression Promotes Osteosarcoma Cell Invasion Via Activation of MEK-ERK Pathway

Cited by 84 publications

References 2 publications

Targeting of COX-2 Expression by Recombinant Adenovirus shRNA Attenuates the Malignant Biological Behavior of Breast Cancer Cells

Targeting of COX-2 Expression by Recombinant Adenovirus shRNA Attenuates the Malignant Biological Behavior of Breast Cancer Cells

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

A risk score model for the prediction of osteosarcoma metastasis

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