Emmanuelle Liaudet-Coopman
  • E-mail :[email]
  • Phone : +33467612423
  • Location : Montpellier, France
Last update 2017-08-22 12:12:51.513

Emmanuelle Liaudet-Coopman PhD Cellular and Molecular Biology

Course and current status

University Education:

  • 2002: HDR
  • 1994: PhD thesis
  • 1988: Chemical Civil Engineer, ENSCM


Professional Cursus

  • 2011: DR2 INSERM
  • 1999: CR1 INSERM
  • 1994-1997: 4 years of post-doctoral training at Lombardi Cancer Center, Washington DC, USA


Main Points of Scientific Activity

  • 2015-2019: Director of the team ‘Proteases, Microenvironment and Cancer’, INSERM U1194, IRCM, Montpellier
  • 2011-2014: Director of the team ‘Cathepsins, Autophagy and Cancer’, INSERM U896, IRCM, Montpellier
  • 2008-2011: Junior Group Leader of the emerging team “Cathepsins, Autophagy and Cancer” INSERM U896, IRCM, Montpellier
  • 2005-2008: Financial for ANR «Jeunes Chercheurs», INSERM U540, Montpellier
  • 1994-1997: 4 years of post-doctoral training. Lombardi Cancer Center, Georgetown University, Washington D.C., USA

Scientific summary

A solid tumor is composed of tumor cells, resident and infiltrating non-tumor cells, and factors secreted in proximity to these cells. This ecosystem can be collectively described as the tumor microenvironment. Both the tumor cells and the neighboring stromal cells communicate in the tumor microenvironment via secreted factors (protease, cytokines, growth factors) acting on receptors on their target cells.

Our research main topic focuses on the roles and action mechanisms of the aspartic protease cathepsin D in cell proliferation, invasion, angiogenesis and apoptosis leading to tumor progression and metastasis. Cathepsin D is a well-established independent marker of poor prognosis for breast cancers, whose overexpression is correlated with the incidence of metastasis. Cathepsin D is overproduced by breast cancer cells and the pro-enzyme is hyper-secreted into the tumor microenvironment. Our team has made major contributions to the understanding of unconventional roles of cathepsin D in the extracellular space and in the cytoplasm of breast cancer. We proved that the cathepsin D overproduced by breast cancer is causally implicated in tumor progression and metastasis. We showed that mutated, catalytically inactive D231N-cathepsin D is still mitogenic active, suggesting a possible role independent of its catalytic function. We highlighted the paracrine role of cathepsin D in the tumor microenvironment. The cathepsin D overproduced and hypersecreted by cancer cells triggers the invasive growth of fibroblasts independently of its catalytic activity. We have shown that secreted cathepsin D promotes mammary fibroblast outgrowth via binding to LDL receptor-related protein-1, LRP, and enhances proteolysis in the breast tumor microenvironment by degrading the cysteine cathepsin inhibitor cystatin C. We also demonstrated that cathepsin D and its LRP1 receptor trigger adipocyte differentiation, one of the most prominent cells in the breast cancers tumor microenvironment. On the other hand, after induced apoptosis, lysosomal cathepsin D is released into the cytoplasm, where it interacts with and/or cleaves pro-apoptotic or anti-apoptotic proteins. We showed that cathepsin D overproduced by cancer cells is released into the cytoplasm and enhances apoptosis-dependent chemosensitivity in apoptosis-induced conditions. More recently, using the yeast two-hybrid screen, we identified nuclear proteins as new cathepsin D partners, suggesting a role of this protease in the nuclei of breast cancer cells.

Project - Our team actively participates in the contemporary highly dynamic field that aims to unravel the non-classical roles of proteases in breast cancer. Our overall goal is to understand how the breast tumor microenvironment, now recognized as an important contributor to the progression of tumor and metastasis, is modulated by the protease cathepsin D. We will develop preclinical mouse models of breast cancer overproducing cathepsin D to study the cross-talk between epithelial and stromal cells during breast cancer progression. We will initiate the targeting of the cathepsin D secreted into the breast tumor microenvironment. We will also use the expertise acquired over the past several years to address two fundamental questions about the atypical function of proteases in breast cancer: the signaling role of extracellular cathepsin D and the significance of the newly described nuclear form of the protease. Mass spectrometry studies of the secretome and yeast-two-hybrid analysis identified new extracellular and nuclear proteins as key targets of cathepsin D in breast cancer. These findings may open up new avenues for personalized breast cancer therapy.

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