HGF induces CXCR4 and CXCL12-mediated tumor invasion through Ets1 and NF-kappaB
Authors: Maria Alfonsina Desiderio
Emanuela Matteucci
Paola Bendinelli
Paola Maroni
Journal: Carcinogenesis (2006)
Discipline: CLINICAL MEDICINE
Keywords: CXCR4; chemokine receptor; metastatic breast cancer; tumor environmental stimuli; hepatocyte growth factor
Affiliations: Institute of General Pathology, School of Medicine University of Milan, via Luigi Mangiagalli, 31-20133 Milan, Italy.

Abstract:  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-kappaB 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-kappaB 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-kappaB activity to enhance the invasive/metastatic phenotype of breast carcinoma cells. 

Retracted: No

PubPeer comments:
 -Carcinogenesis 28. The shape of the bands depends on the run in the gel. So the bands are not the same. - Figure 2A Mol Cancer Res 7 and Carcinogenesis 28: The RNA 18S and 28S in the yellow square were only illustrative of RNA visualization. - The experiments are repeated three times. , 
 #3  Figure 2A Mol Cancer Res 7 and Carcinogenesis 28: The RNA 18S and 28S in the yellow square were only illustrative of RNA visualization. What do you mean by  only illustrative of RNA visualization ? , 
 #4 The levels of 36B4, the housekeeping gene, are shown and they are used for the evaluation of the RNA loading in the gel. Thus, 18 and 28S are only exemplificative of the run. , 
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 *[Left]*, Figure 4B (detail at lower right) -  Western blot analysis of total and nuclear proteins prepared from HGF- or hypoxia-treated MCF-7 cells . Please compare with *[at right]* part of Fig 1D from [Maroni et al (2015)] , for MDA-MB231 cells. ![file] The lanes should not be similar, yet they are. , 
 I have another concern about Fig 4B. Fragments of the Vinculin band seem to reappear in at least seven subsequent papers, ensuring equal lane loading across many different sets of conditions. ![file] , 
 #3  Figure 2A Mol Cancer Res 7 and Carcinogenesis 28: The RNA 18S and 28S in the yellow square were only illustrative of RNA visualization. If these diagrams are artists conceptions rather than actual experimental results, shouldn t they have been labelled as such? Back at #1, Peer 2 noted the recurring features along the top and bottom edges of each blob. ![] But the background texture in each lane, **between** the 18S and 28S blobs, also recurs, with a pattern of diagonal stripes that s visible at increased lightness. Figure 1A: ![file] Similar diagonal-streak textures exist in the lanes of Fig 2A: ![file] Now it is tempting to focus on similarities in the arrangements of Figs 1A and 2A - the sequences of vertical displacements of lanes - and wonder at their connections. I am also wondering, though, how many original lanes were required for these  illustrations of RNA visualization ? ![file] ,