References of "Polette, Myriam"
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See detailDose-dependent effect of Estetrol on Angiogenesis and Tumor Growth
Gallez, Anne ULiege; Blacher, Silvia ULiege; Lenfant, Françoise et al

Poster (2017, April 24)

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and ... [more ▼]

Hormone replacement therapies (HRT) based on estrogen preparations are the most powerful treatments to prevent menopause symptoms. However, they are associated to an increased risk of breast cancer and they sustain the development of Estrogen Receptor α-positive tumors (ERα+). In addition, we have previously observed that estradiol (E2) can promote the growth of ERα-negative (ERα-) tumors, by increasing tumor angiogenesis that subsequently improves oxygen and nutrients delivery, thereby preventing hypoxia and necrosis. To identify new and safe drugs for the development of HRT presenting a better benefit/risk ratio, it is therefore necessary to evaluate the potential impact of new candidates on both ERα+ and ERα- tumors. In this context, estetrol (E4), a natural estrogen exclusively produced by the fetal liver, is a promising candidate. [less ▲]

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See detailZonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.
Lesage, Julien; Suarez-Carmona, Meggy; Neyrinck-Leglantier, Deborah et al

in FASEB Journal (2017), 31(4), 1678-1688

Zonula occludens-1 (ZO-1) is a submembrane scaffolding protein that may display proinvasive functions when it relocates from tight junctions into the cytonuclear compartment. This article examines the ... [more ▼]

Zonula occludens-1 (ZO-1) is a submembrane scaffolding protein that may display proinvasive functions when it relocates from tight junctions into the cytonuclear compartment. This article examines the functional involvement of ZO-1 in CXCL8/IL-8 chemokine expression in lung and breast tumor cells. ZO-1 small interfering RNA and cDNA transfection experiments emphasized regulation of CXCL8/IL-8 expression via a cytonuclear pool of ZO-1. Luciferase reporter assays highlighted a 173-bp region of CXCL8/IL-8 promoter that responded to ZO-1. Moreover, by using mutated promoter constructs, we identified a NF-κB site as critical in this activation. Furthermore, NF-κB pathway signaling analysis revealed both IκBα and p65 phosphorylation in ZO-1-overexpressing cells, and subsequent p65 silencing validated its requirement for CXCL8/IL-8 induction. Investigation of the functional implication of this regulatory axis next showed the proangiogenic activity of ZO-1 in both ex vivo and in vivo angiogenesis assays. Finally, we found that non-small-cell lung carcinoma that presented a cytonuclear ZO-1 pattern was significantly more angiogenic that that without detectable cytonuclear ZO-1 expression. Taken together, our results demonstrate that ZO-1 regulates CXCL8/IL-8 expression via the NF-κB signaling pathway and its p65 subunit, which subsequently modulates the transcription of IL-8. We also provide evidence of a newly identified regulatory pathway that could promote angiogenesis. Thus, our results support the concept that the ZO-1 shuttle from the cell junction to the cytonuclear compartment may affect both the intrinsic invasive properties of tumor cells and the establishment of the protumoral microenvironment. [less ▲]

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See detailEpithelial-Mesenchymal Plasticity and Circulating Tumor Cells: Travel Companions to Metastases
Francart, Marie-Emilie ULiege; Lambert, Justine ULiege; Vanwynsberghe, Aline ULiege et al

in Developmental Dynamics : An Official Publication of the American Association of Anatomists (2017)

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See detailTissue factor induced by epithelial-mesenchymal transition triggers a pro-coagulant state that drives metastasis of circulating tumor cells.
Bourcy, Morgane ULiege; Suarez-Carmona, Meggy ULiege; Lambert, Justine ULiege et al

in Cancer Research (2016)

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific ... [more ▼]

Epithelial-mesenchymal transition (EMT) is prominent in circulating tumor cells (CTC), but how it influences metastatic spread in this setting is obscure. Insofar as blood provides a specific microenvironment for tumor cells, we explored a potential link between EMT and coagulation that may provide EMT-positive CTC with enhanced colonizing properties. Here we report that EMT induces tissue factor (TF), a major cell-associated initiator of coagulation and related pro-coagulant properties in the blood. TF blockade by antibody or shRNA diminished the pro-coagulant activity of EMT-positive cells, confirming a functional role for TF in these processes. Silencing the EMT transcription factor ZEB1 inhibited both EMT-associated TF expression and coagulant activity, further strengthening the link between EMT and coagulation. Accordingly, EMT-positive cells exhibited a higher persistance/survival in the lungs of mice colonized after intravenous injection, a feature diminished by TF or ZEB1 silencing. In tumor cells with limited metastatic capability, enforcing expression of the EMT transcription factor Snail increased TF, coagulant properties and early metastasis. Clinically, we identified a subpopulation of CTC expressing vimentin and TF in the blood of metastatic breast cancer patients consistent with our observations. Overall, our findings define a novel EMT-TF regulatory axis which triggers local activation of coagulation pathways to support metastatic colonization of EMT-positive CTC. [less ▲]

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See detailSoluble factors regulated by epithelial-mesenchymal transition mediate tumour angiogenesis and myeloid cell recruitment.
Suarez-Carmona, Meggy ULiege; Bourcy, Morgane ULiege; LESAGE, J et al

in Journal of Pathology (The) (2015), 236(4), 491-504

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been ... [more ▼]

Epithelial-to-mesenchymal transition (EMT) programs provide cancer cells with invasive and survival capacities that might favor metastatic dissemination. Whilst signaling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumor cells and the tumor microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumor. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumors presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumors with little or no EMT. Taken together, our results show that EMT programs trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favor cancer spread. [less ▲]

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See detailFhit regulates EMT targets through an EGFR/Src/ERK/Slug signaling axis in human bronchial cells.
Joannes, Audrey; Grelet, Simon; Duca, Laurent et al

in Molecular Cancer Research (2014), 12(5), 775-83

In many cancers, including lung carcinomas, Fragile histidine triad (Fhit) is frequently decreased or lost. Fhit status has recently been shown to be associated with elevated in vitro and in vivo ... [more ▼]

In many cancers, including lung carcinomas, Fragile histidine triad (Fhit) is frequently decreased or lost. Fhit status has recently been shown to be associated with elevated in vitro and in vivo invasiveness in lung cancer. Tumor cell invasion is facilitated by epithelial-mesenchymal transition (EMT), a process by which tumor cells lose their epithelial features to acquire a mesenchymal cell-like phenotype. In this study, the mechanism underlying Fhit-regulated EMT was deciphered. Using Slug knockdown, pharmacologic inhibitors PD98059, PP1, and gefitinib as well as an anti-EGFR antibody, it was demonstrated that Fhit silencing in bronchial cells induced overexpression of two primary EMT-associated targets, MMP-9 and vimentin, to regulate cell invasion dependent on an EGFR/Src/ERK/Slug signaling pathway. Moreover, ectopic expression of Fhit in Fhit-deficient lung cancer cells downregulated this pathway. Finally, an inverse correlation was observed between Fhit and phospho-EGFR levels in a cohort of human squamous cell lung carcinoma specimens. These results demonstrate a Fhit-dependent mechanism in the control of EMT-regulated EGFR signaling. IMPLICATIONS: This study adds new insight into the regulatory mechanism of EMT, a process known to increase resistance to conventional and targeted therapies in lung cancer. [less ▲]

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See detailRegulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells.
Luczka, E.; Syne, Laïdya ULiege; Nawrocki-Raby, B. et al

in Clinical & Experimental Metastasis (2013), 30(7), 833-843

During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell ... [more ▼]

During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell-cell adhesion complexes such as tight junctions (TJs). TJs are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). We here evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, we showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. In addition, in vitro, the localization of ZO-2 varied according to invasive properties of tumor cells, with a cytoplasmic localization correlating with invasion. In addition, we demonstrated that ZO-2 inhibition increases invasive and migrative capacities of invasive tumor cells. This was associated with an increase of MT1-MMP. These results suggest that ZO-2, besides its structural role in tight junction assembly, can act also as a repressor of tumor progression through its ability to reduce the expression of tumor-promoting genes in invasive tumor cells. [less ▲]

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See detailVimentin expression predicts the occurrence of metastases in non small cell lung carcinomas.
Dauphin, Maryline; Barbe, Coralie; Lemaire, Sarah et al

in Lung Cancer (2013), 81(1), 117-22

Epithelial-to-mesenchymal transition (EMT) is believed to contribute to tumour invasion. Vimentin expression by carcinoma cells is a largely recognized marker of EMT. This study aimed at examining ... [more ▼]

Epithelial-to-mesenchymal transition (EMT) is believed to contribute to tumour invasion. Vimentin expression by carcinoma cells is a largely recognized marker of EMT. This study aimed at examining vimentin expression in non small cell lung carcinomas (NSCLC) by immunohistochemistry to evaluate potential correlations between vimentin expression and the differentiation status, the TNM stage and the outcome of the patients. 295 NSCLC including 164 squamous cell carcinomas (SCC), 108 adenocarcinomas (AC) and 23 other NSCLC carcinomas have been examined by immunohistochemistry. Vimentin was indeed detected in 145 cases (49.2%). It was principally present in isolated tumour cells and invasive clusters, particularly in cells at the tumour/stroma interface. Vimentin expression was significantly more expressed in large cell neuroendocrine, adeno-squamous and sarcomatoid carcinomas than in SCC and AC and was significantly associated with the differentiation status of carcinomas. The follow-up of 193 patients further demonstrated that an extensive expression of vimentin (>50% of tumour cells) was associated with the occurrence of metastases. In conclusion, our data demonstrate that vimentin expression is a frequent event in NSCLC and that its expression can be associated with a lack of differentiation and the occurrence of metastases. [less ▲]

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