References of "Paye, Alexandra"
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See detailDynamics of Internalization and Recycling of the Pro-Metastatic Membrane Type 4-Matrix Metalloproteinase (MT4-MMP) in Breast Cancer Cells
Truong, Alice ULg; Yip, Cassandre ULg; PAYE, Alexandra ULg et al

in FEBS Journal (2016), 283(4), 704-22

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes ... [more ▼]

MT4-MMP (MMP17) is a glycosylphosphatidyl inositol (GPI)-anchored membrane-type MMP expressed on the cell surface of human breast cancer cells. In triple negative breast cancer cells, MT4-MMP promotes primary tumor growth and lung metastases. Although trafficking and internalization of the transmembrane MT1-MMP have been extensively investigated, little is known about the regulatory mechanisms of the GPI-anchored MT4-MMP. Here, we investigated the fate and cellular trafficking of MT4-MMP by analyzing its homophilic complex interactions, internalization and recycling dynamics compared to an inert form, MT4-MMP-E249A. Oligomeric and dimeric complexes were analyzed by co-transfection of cells with FLAG- or Myc-tagged MT4-MMP by reducing and non-reducing immunoblots and co-immunoprecipitation experiments. The trafficking of MT4-MMP was studied using an antibody feeding assay and confocal microscopy analysis or cell surface protein biotinylation and Western blot analysis. We demonstrate that MT4-MMP forms homophilic complexes at the cell surface, internalizes in early endosomes, and some of the enzyme is either auto-degraded or recycled to the cell surface. Our data indicate that MT4-MMP is internalized by the CLIC/GEEC pathway, a mechanism that differs from other MT-MMP members. Although MT4-MMP localizes with caveolin-1, MT4-MMP internalization was not affected by inhibitors of caveolin-1 or clathrin endocytosis pathways but was reduced by cdc42 or RhoA silencing with siRNA. We provide a new mechanistic insight into the regulatory mechanisms of MT4-MMP, which may have implications in the design of novel therapeutic strategies for metastatic breast cancer. This article is protected by copyright. All rights reserved. [less ▲]

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See detailDynamics of Internalization and Recycling of the pro-Metastatic Membrane Type 4-Matrix Metalloproteinase (MT4-MMP) in Breast Cancer cells
Truong, Alice ULg; Yip, Cassandre ULg; PAYE, Alexandra ULg et al

Poster (2015, October 26)

MT4-MMP (MMP17) is a glycosyl-phosphatidyl inositol-anchored membrane-type matrix metalloproteinase expressed at the cell surface of human breast cancer cells. In triple negative breast cancer, MT4-MMP ... [more ▼]

MT4-MMP (MMP17) is a glycosyl-phosphatidyl inositol-anchored membrane-type matrix metalloproteinase expressed at the cell surface of human breast cancer cells. In triple negative breast cancer, MT4-MMP promotes primary tumor growth and lung metastases. Recently, we demonstrated that EGFR activation and signaling are enhanced by MT4-MMP in a non-proteolytic dependent manner. While trafficking and internalization of EGFR was extensively investigated, little is known about MT4-MMP. Here, we investigated the dimerization, internalization and recycling dynamics of MT4-MMP and its mutated inactive form MT4-MMP-E249A. We demonstrate that MT4-MMP forms dimers and oligomers at the cell surface, a process that was not inhibited neither by broad-spectrum MMP inhibitors (GM6001 and BB94) nor TIMP-2. MT4-MMP is internalized in early endosomes from 10 minutes to 60 minutes. Once internalized, some amount of MT4-MMP is auto-degraded, whereas its inert form E249A was found intact. Large part of the internalized enzyme was recycled intact at the cell surface. By exploring its endocytosis, we found that MT4-MMP is internalized by the CLIC/GEEC pathway, a mechanism that differs from other MT-MMP members. Overall, we provided a new mechanistic insight on the regulatory mechanisms of MT4-MMP in human breast cancer cells. We also, highlighted unique features of MT4-MMP among membrane-associated MMPs, which may be useful for the design of novel therapeutic strategies for metastatic breast cancer. [less ▲]

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See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2015, September 11)

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See detailCombination treatment of cancer
PAYE, Alexandra ULg; Sounni, Nor Eddine ULg; NOEL, Agnès

Patent (2015)

The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is ... [more ▼]

The present invention provides MT4-MMP inhibitor and EGFR inhibitor for use in the treatment of cancer, wherein said MT4-MMP inhibitor and EGFR inhibitor are different from each other. MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol (GPI) anchored MMP produced by cancer cells that promotes tumor vascularization and metastases. The present invention found that MT4-MMP expression promotes cancer cell proliferation. These effects involve retinoblastoma protein (Rb) inactivation, cyclin dependent kinase CDK4 activation and Epidermal Growth Factor Receptor (EGFR) signaling. Co-immuno-precipitations indicate the existence of protein complexes harboring MT4-MMP and EGFR. The present invention further found a novel mechanism of MT4-MMP action through an outside-in signaling involving EGFR. An unexpected crosstalk between an MMP and EGFR was identified and recognized as a key driver of cancer cell biology. [less ▲]

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See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2015, June)

Detailed reference viewed: 23 (1 ULg)
See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2015, February 11)

Detailed reference viewed: 19 (6 ULg)
See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2015, January 31)

Detailed reference viewed: 18 (6 ULg)
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See detailEGFR activation and signaling in cancer cells are enhanced by the membrane-bound metalloprotease MT4-MMP.
Paye, Alexandra ULg; Truong, Alice ULg; Yip, Cassandre ULg et al

in Cancer Research (2014), 74(23), 6758-70

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of ... [more ▼]

MT4-MMP (MMP-17) is a GPI-anchored matrix metalloprotease expressed on the surface of cancer cells which promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein (Rb) inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGF- and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expression were correlated in human triple negative breast cancer specimens. Altogether our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. [less ▲]

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See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2014, September 30)

Detailed reference viewed: 14 (5 ULg)
See detailClinical significance of MT4-MMP and EGFR expression in Breast Cancer
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2014, May 19)

Detailed reference viewed: 18 (3 ULg)
See detailStudy of the pro-tumoral effects of MT4-MMP
Yip, Cassandre ULg; PAYE, Alexandra ULg; Truong, Alice ULg et al

Scientific conference (2014, January 27)

Detailed reference viewed: 14 (3 ULg)