Src Induces <i>Urokinase Receptor</i> Gene Expression and Invasion/Intravasation via Activator Protein-1/p-c-Jun in Colorectal Cancer

Leupold, Jörg Hendrik; Asangani, Irfan A.; Maurer, Gabriele D.; Lengyel, Ernst; Post, S.; Allgayer, Heike

doi:10.1158/1541-7786.mcr-06-0211

Cited by 35 publications

(45 citation statements)

References 53 publications

(59 reference statements)

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“…After 24 h, noninvading cells were removed with cotton swabs. Invaded cells were trypsinized and counted using the ATPluminescence-based motility-invasion assay (22).…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear extracts, electrophoretic mobility shift assays, and Supershift using u-PAR promoter sequence GTGATCACAACTCCATGAGTCAGGGCCGAG-3 ¶ including activator protein (AP-1; À190/À171), and chromatin immunoprecipitation (ChIP) analyses were performed as described (22). Briefly, cells were plated and starved for 48 h. After Cetuximab pretreatment (4 h) and 1-h EGF stimulation, cells were fixed (1%formaldehyde/10 min), lysed, and the genomic DNA sheared to 300 bp-1.5 kb.…”

Section: Methodsmentioning

confidence: 99%

“…ChIP with 2 Ag specific (p-c-Jun, JunD) and nonspecific IgG was done overnight using aliquots of precleared lysates. The primer set for final PCR was used as described (22). A control primer set amplifying a region 2,000 bp upstream of the u-PAR transcription start site, lacking AP-1site, was applied for negative control amplification and did not show enrichment.…”

Section: Methodsmentioning

confidence: 99%

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Cetuximab Attenuates Metastasis and u-PAR Expression in Non–Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity

et al. 2009

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Cetuximab, which blocks ligand binding to epidermal growth factor receptor (EGFR), is currently being studied as a novel treatment for non-small cell lung cancer (NSCLC). However, its mechanisms of action toward metastasis, and markers of drug sensitivity, have not been fully elucidated. This study was conducted to (a) determine the effect of Cetuximab on invasion and NSCLC-metastasis; (b) investigate urokinase-type plasminogen activator receptor (u-PAR), a major molecule promoting invasion and metastasis, as a target molecule; (c) delineate molecular mediators of Cetuximab-induced metastasis inhibition; and (d) identify biomarkers of drug sensitivity in NSCLC. Cetuximab treatment resulted in reduced growth and Matrigel invasion of H1395 and A549 NSCLC cell lines, in parallel with reduced u-PAR mRNA and protein.

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“…After 24 h, noninvading cells were removed with cotton swabs. Invaded cells were trypsinized and counted using the ATPluminescence-based motility-invasion assay (22).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cetuximab Attenuates Metastasis and u-PAR Expression in Non–Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity

et al. 2009

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“…To study the effect of MZF1 overexpression on in vivo tumor formation and metastasis, we used the chicken-embryo-metastasis assay (CAM), which is able to differentiate primary tumor growth, intravasation, and metastasis in a highly sensitive and quantitative in vivo setting (35). Rko cells transfected with pCDNA3-vector, or with pCDNA3-MZF1, were inoculated on the upper CAM of 10-day old chicken embryos, and chicken embryos were grown for 7 more days.…”

Section: In Vivomentioning

confidence: 99%

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Mudduluru

Vajkoczy

Allgayer

2010

Molecular Cancer Research

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Myeloid zinc finger 1 (MZF1) is a member of the SCAN domain family transcription factors that form dimers through their highly conserved SCAN motifs. Silencing of MZF1 inhibits cell proliferation, and abnormal expression of MZF1 results in cancer development. However, a potential role of MZF1 in metastasis remains unclear. Axl is a receptor tyrosine kinase and was first identified as a transforming gene in chronic myeloid leukemia. Axl overexpression induces proliferation, migration, and invasion and is highly expressed in different human cancers. In this study, we show that overexpression of MZF1 induces migration and invasion in colorectal (Rko, SW480) and cervical (HeLa) cancer cells. In addition, we show that MZF1 binds to the Axl promoter, transactivates promoter activity, and enhances Axl-mRNA and protein expression in a dose-dependent manner. In vitro, sh-RNA knockdown of Axl reduced MZF1-induced migration and invasion in HeLa and Rko cells (P = 0.05). Additionally, Rko cells overexpressing MZF1 showed increased tumor formation and liver metastasis in the chicken-embryo-metastasis assay in vivo. Furthermore, the expression of MZF1 and Axl was significantly higher in resected colorectal tumors compared with corresponding normal tissues (P = 0.02; P = 0.05), and MZF1 expression was positively correlated with Axl gene expression in tumor tissues (P < 0.01). Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. Mol Cancer Res; 8(2); 159-69. ©2010 AACR.

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“…To date a number of molecular steps have been described; they involve matrix metalloproteinases and interaction between cancer cells and endothelial adhesion molecules [34]. It has been reported that the urokinase plasminogen activator (u-PA) plays a decisive role in colorectal cancer intravasation [36], as it binds to its receptor (u-PAR) and then activates plasminogen and other proteases, such as, for example, matrix metalloproteinases-2 (MMP-2) and MMP-9. All this adds to the breakdown of the ECM, which, in turn, contributes to intravasation.…”

Section: Pathway Of Colorectal Liver Metastasismentioning

confidence: 99%

Tumour Microenvironment: Overview with an Emphasis on the Colorectal Liver Metastasis Pathway

Giakoustidis

Mudan

Hagemann

2014

Cancer Microenvironment

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The tumour microenvironment (TME) represents a dynamic network that plays an important role in tumour initiation, proliferation, growth, and metastasis. Cell behaviour may be regulated by interplay of molecular interactions involving positive and negative reinforcement as well as a high level of cross-talk, which determines this system. Additionally, cancer involves cell proliferation, its malignancy defined by the tumour's ability to break down normal tissue architecture and by a dynamic process of invasion and metastasis. The metastatic cascade is regulated by a chain of molecular steps which triggers the progression of the developing cancer cell in the primary tumour into a number of transformations, leading to invasion and proceeding to metastases. Tumour-associated macrophages (TAMs) play a key-role in the progression from inflammatory conditions to cancer; TAMs are also capable of infiltrating the tumour microenvironment. Furthermore, myeloid-derived suppressor cells (MDSCs), a population of inhibitory immune cells, have been reported to increase in various cancer types, although characterising human MDSCs remains difficult, as their phenotype is quite variable. The future of cancer treatment is likely to involve creating more drugs that target these elements as well as others. An overview of the tumour's microenvironment is, therefore, presented in this paper, focusing on the metastatic pathways of primary colorectal cancer to the liver.

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Src Induces Urokinase Receptor Gene Expression and Invasion/Intravasation via Activator Protein-1/p-c-Jun in Colorectal Cancer

Abstract: The urokinase receptor [urokinase plasminogen activator receptor (u-PAR)] promotes invasion and metastasis and is associated with poor patient survival.

Cited by 35 publications

References 53 publications

Cetuximab Attenuates Metastasis and u-PAR Expression in Non–Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity

Cetuximab Attenuates Metastasis and u-PAR Expression in Non–Small Cell Lung Cancer: u-PAR and E-Cadherin are Novel Biomarkers of Cetuximab Sensitivity

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Tumour Microenvironment: Overview with an Emphasis on the Colorectal Liver Metastasis Pathway

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