Journal Article

HGF induces CXCR4 and CXCL12-mediated tumor invasion through Ets1 and NF-κB

Paola Maroni, Paola Bendinelli, Emanuela Matteucci and Maria Alfonsina Desiderio

in Carcinogenesis

Volume 28, issue 2, pages 267-279
Published in print July 2006 | ISSN: 0143-3334
Published online February 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl129
HGF induces CXCR4 and CXCL12-mediated tumor invasion through Ets1 and NF-κB

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CXCR4 is a chemokine receptor probably involved in the homing of metastatic breast cancer, and its expression is modulated by tumor environmental stimuli such as hepatocyte growth factor (HGF) and hypoxia. Here, we demonstrate that, depending on the stimulus, different transcription factors can cooperate in enhancing CXCR4 transcription in MCF-7 breast cancer cell line. In HGF-treated MCF-7 cells, the DNA binding of Ets1 activated by MAPK1/ERK1/2 transduction pathway as well as the DNA binding of NF-κB played a critical role in CXCR4 transcription and protein induction. Under HGF stimulation, the blockade of these transcription factors by dominant negatives and inhibitors prevented the expression of CXCR4 receptor, the activity of a gene reporter driven by CXCR4 promoter sequence and the chemoinvasion toward the CXCL12 ligand. NF-κB was activated also by hypoxia and contributed, with HIF-1, to the increase in CXCR4 expression. The results suggest that Ets1, specifically activated by HGF, might cooperate with NF-κB activity to enhance the invasive/metastatic phenotype of breast carcinoma cells.

Journal Article.  7706 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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