What's new in U908
Paper Accepted! January 2015
NGF induces TrkA-CD44 interaction to increase tumor aggressiveness
Paper Accepted! February 2015
First proof of NGF/ProNGF effects on CSCs!
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Pink Ruban Award
Join us to congratulate Dr. Lagadec for his Pink Ruban Award 2014!
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Welcom to INSERM U908 Website
Lab' director Edito : Pr. Xuefen Le Bourhis
INSERM U908 Laboratory, from basic research to bed side
Despite considerable progress in fundamental and clinical researches, current anti-cancer therapies consist mainly in tumor removal and/or destruction of the tumoral cells using radiotoxic and chemotoxic strategies. Unfortunately, cancers often become refractory to these treatments and patients are left with few or no treatment alternatives. Our objective is to better define molecular mechanisms driving tumor aggressiveness and therapy resistances. We aim to identify potential prognostic markers and to propose more efficient therapeutic strategies.
Profile of activities
Our project includes three complementary axes, based on our recent findings and technological developments :
We were the first to show the implication of neurotrophins in breast cancer; our ongoing works reveal that tumorigenesis and resistance to therapeutic agents vary according to the recruitment of different signaling platforms by neurotrophins receptors. We will a) determine the signaling and the impact of neurotrophins receptors platforms in the acquisition of cancer cell aggressiveness; b) evaluate the potential of neurotrophins receptors platforms as prognostic markers and/or therapeutic targets.
Axe 2. Role of epigenetic effectors such as Polycomb group (PcG) proteins in the regulation of cancer cell plasticity.
Increasing data describe the pivotal role played by proteins of polycomb repression complexes such as Bmi1 and Ezh2 in cell proliferation and differentiation of both normal and tumor cells. We will a) characterize PcG proteins expression pattern in human cancer cells and in a mouse mammary tumorigenesis model; b) determine the involvement of PcG proteins in the control of cancer cell plasticity and resistance to conventional therapies.
Axe 3. Identification of molecular mechanisms involved in therapy-induced cancer stem cell (CSC) reprogramming.
We will a) evaluate how anticancer treatments modulates the production of soluble factors (such as growth factors/cytokines/chemokines) that induce non-CSCs into CSCs reprogramming; b) assess the involvement of intrinsic factors such PcG proteins in CSCs reprogramming; c) target the identified factors to prevent treatment-induced reprogramming in an in vivo context using transgenic mice.
Our major papers
Role of p75 neurotrophin receptor in stem cell biology: more than just a marker.
Tomellini E, Lagadec C, Polakowska R, Le Bourhis X.
Cell Mol Life Sci. 2014 Jan 31.
The in vivo performance of ferrocenyl tamoxifen lipid nanocapsules in xenografted triple negative breast cancer.
Lainé AL, Adriaenssens E, Vessières A, Jaouen G, Corbet C, Desruelles E, Pigeon P, Toillon RA, Passirani C.
Biomaterials. 2013 Sep;34(28):6949-56. doi: 10.1016/j.biomaterials.2013.05.065.
Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein.
Demont Y, Corbet C, Page A, Ataman-Önal Y, Choquet-Kastylevsky G, Fliniaux I, Le Bourhis X, Toillon RA, Bradshaw RA, Hondermarck H.
J Biol Chem. 2012 Jan 13;287(3):1923-31. doi: 10.1074/jbc.M110.211714. Epub 2011 Nov 29.
Brain-derived neurotrophic factor and neurotrophin-4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival.
Vanhecke E, Adriaenssens E, Verbeke S, Meignan S, Germain E, Berteaux N, Nurcombe V, Le Bourhis X, Hondermarck H.
Clin Cancer Res. 2011 Apr 1;17(7):1741-52. doi: 10.1158/1078-0432.CCR-10-1890.
TrkA overexpression enhances growth and metastasis of breast cancer cells.
Lagadec C, Meignan S, Adriaenssens E, Foveau B, Vanhecke E, Romon R, Toillon RA, Oxombre B, Hondermarck H, Le Bourhis X.
Oncogene. 2009 May 7;28(18):1960-70. doi: 10.1038/onc.2009.61.