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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Added by liaudet-coopman
Group name EquipeELC
Item Type Journal Article
Title Alteration of cathepsin D trafficking induced by hypoxia and extracellular acidification in MCF-7 breast cancer cells
Creator Achour et al.
Author Oussama Achour
Author Yahya Ashraf
Author Nicolas Bridiau
Author Meriem Kacem
Author Nicolas Poupard
Author Stéphanie Bordenave-Juchereau
Author Frédéric Sannier
Author Nathalie Lamerant-Fayel
Author Claudine Kieda
Author Emmanuelle Liaudet-Coopman
Author Jean-Marie Piot
Author Thierry Maugard
Author Ingrid Fruitier-Arnaudin
Abstract The microenvironment that surrounds tumor cells is characterized by hypoxic conditions and extracellular acidity. These hostile conditions induce crucial changes in cell behavior and can promote the secretion of many soluble factors such as growth factors, cytokines and enzymes. The lysosomal aspartyl-endopeptidase cathepsin D (CD) is a marker of poor prognosis in breast cancer and is associated with a metastatic risk. In this study, the transport of CD was investigated in a model of breast cancer cells line (MCF-7) cultivated under hypoxia and acidification of media. CD secretion was assessed using Western blot analysis and protease activity was measured in conditioned culture media. We demonstrate that cultured MCF-7 cells secrete an active 52 kDa pCD precursor and report that under hypoxia there was an increased amount of pCD secreted. More surprisingly, extracellular acidification (pH 6 and 5.6) induced the secretion of the fully-mature and active (34 kDa + 14 kDa) double chain CD. Our findings reflect the fact that chemical anomalies influence the secretion path of CD in a breast cancer cell model, resulting in altered trafficking of the mature form. This important result may provide new arguments in favor of the role of extracellular CD in the degradation of the matrix proteins that constitute the breast tumor microenvironment.
Publication Biochimie
Volume 121
Pages 123-130
Date Feb 2016
Journal Abbr Biochimie
Language eng
DOI 10.1016/j.biochi.2015.11.007
ISSN 1638-6183
Library Catalog PubMed
Extra PMID: 26582416
Tags Acidification, Breast Neoplasms, Cathepsin D, Cell Hypoxia, Cell Movement, Female, Humans, Kinetics, MCF-7 Cells, original, Pro-cathepsin D, Proteolytic activity
Date Added 2018/09/26 - 14:32:47
Date Modified 2019/05/29 - 12:08:09


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