Biologie du cancer du sein


Année de publication : 2010

Aurore Toullec, Damien Gerald, Gilles Despouy, Brigitte Bourachot, Melissa Cardon, Sylvain Lefort, Marion Richardson, Guillem Rigaill, Maria-Carla Parrini, Carlo Lucchesi, Dorine Bellanger, Marc-Henri Stern, Thierry Dubois, Xavier Sastre-Garau, Olivier Delattre, Anne Vincent-Salomon, Fatima Mechta-Grigoriou (2010 Jun 11)

Oxidative stress promotes myofibroblast differentiation and tumour spreading.

EMBO molecular medicine : 211-30 : DOI : 10.1002/emmm.201000073 En savoir plus

JunD regulates genes involved in antioxidant defence. We took advantage of the chronic oxidative stress resulting from junD deletion to examine the role of reactive oxygen species (ROS) in tumour development. In a model of mammary carcinogenesis, junD inactivation increased tumour incidence and revealed an associated reactive stroma. junD-inactivation in the stroma was sufficient to shorten tumour-free survival rate and enhance metastatic spread. ROS promoted conversion of fibroblasts into highly migrating myofibroblasts through accumulation of the hypoxia-inducible factor (HIF)-1alpha transcription factor and the CXCL12 chemokine. Accordingly, treatment with an antioxidant reduced the levels of HIF and CXCL12 and numerous myofibroblast features. CXCL12 accumulated in the stroma of HER2-human breast adenocarcinomas. Moreover, HER2 tumours exhibited a high proportion of myofibroblasts, which was significantly correlated to nodal metastases. Interestingly, this subset of tumours exhibited a significant nuclear exclusion of JunD and revealed an associated oxido-reduction signature, further demonstrating the relevance of our findings in human cancers. Collectively, our data uncover a new mechanism by which oxidative stress increases the migratory properties of stromal fibroblasts, which in turn potentiate tumour dissemination.


Année de publication : 2009

Tatiana Popova, Elodie Manié, Dominique Stoppa-Lyonnet, Guillem Rigaill, Emmanuel Barillot, Marc Henri Stern (2009 Nov 12)

Genome Alteration Print (GAP): a tool to visualize and mine complex cancer genomic profiles obtained by SNP arrays.

Genome biology : R128 : DOI : 10.1186/gb-2009-10-11-r128 En savoir plus

We describe a method for automatic detection of absolute segmental copy numbers and genotype status in complex cancer genome profiles measured with single-nucleotide polymorphism (SNP) arrays. The method is based on pattern recognition of segmented and smoothed copy number and allelic imbalance profiles. Assignments were verified by DNA indexes of primary tumors and karyotypes of cell lines. The method performs well even for poor-quality data, low tumor content, and highly rearranged tumor genomes.

Floria Lizárraga, Renaud Poincloux, Maryse Romao, Guillaume Montagnac, Gaëlle Le Dez, Isabelle Bonne, Guillem Rigaill, Graça Raposo, Philippe Chavrier (2009 Mar 12)

Diaphanous-related formins are required for invadopodia formation and invasion of breast tumor cells.

Cancer research : 2792-800 : DOI : 10.1158/0008-5472.CAN-08-3709 En savoir plus

Proteolytic degradation of the extracellular matrix by metastatic tumor cells is initiated by the formation of invadopodia, i.e., actin-driven filopodia-like membrane protrusions endowed with matrix-degradative activity. A signaling cascade involving neural Wiskott-Aldrich syndrome protein and the Arp2/3 actin nucleating complex is involved in actin assembly at invadopodia. Yet, the mechanism of invadopodia formation is poorly understood. Based on their role as actin nucleators in cytoskeletal rearrangements, including filopodia formation, we examined the function of Diaphanous-related formins (DRF) in invadopodia formation and invasion by breast tumor cells. Using small interfering RNA silencing of protein expression in highly invasive MDA-MB-231 breast adenocarcinoma cells, we show that three members of the DRF family (DRF1-DRF3) are required for invadopodia formation and two-dimensional matrix proteolysis. We also report that invasion of a three-dimensional Matrigel matrix involves filopodia-like protrusions enriched for invadopodial proteins, including membrane type 1 matrix metalloproteinase, which depend on DRFs for their formation. These data identify DRFs as critical components of the invasive apparatus of tumor cells in two-dimensional and three-dimensional matrices and suggest that different types of actin nucleators cooperate during the formation of invadopodia.


Année de publication : 2008

Bérengère Marty, Virginie Maire, Eléonore Gravier, Guillem Rigaill, Anne Vincent-Salomon, Marion Kappler, Ingrid Lebigot, Fathia Djelti, Audrey Tourdès, Pierre Gestraud, Philippe Hupé, Emmanuel Barillot, Francisco Cruzalegui, Gordon C Tucker, Marc-Henri Stern, Jean-Paul Thiery, John A Hickman, Thierry Dubois (2008 Dec 6)

Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells.

Breast cancer research : BCR : R101 : DOI : 10.1186/bcr2204 En savoir plus

Basal-like carcinomas (BLCs) and human epidermal growth factor receptor 2 overexpressing (HER2+) carcinomas are the subgroups of breast cancers that have the most aggressive clinical behaviour. In contrast to HER2+ carcinomas, no targeted therapy is currently available for the treatment of patients with BLCs. In order to discover potential therapeutic targets, we aimed to discover deregulated signalling pathways in human BLCs.