Dr. Sophie Tartare-Deckert - The role of extracellular matrix in melanoma cell plasticity and resistance to targeted therapy - IPBS-Toulouse, Seminar Room

Sophie Tartare-Deckert

Centre Méditerranéen de Médecine Moléculaire (C3M), Université Côte-d’Azur, Nice, France

The role of extracellular matrix in melanoma cell plasticity and resistance to targeted therapy

Our laboratory is interested in understanding microenvironmental influences and signaling networks that drive tumor growth and dissemination. We have been particularly involved in studying the role of tumor microenvironment in metastatic niche formation and response to therapies in melanoma, the most aggressive and lethal form of skin cancers. The matricellular protein SPARC is an important driver of theses processes, particularly by inducing mesenchymal transition, tumor cell extravasation and p53-dependent survival. Our current work focuses in deciphering how the extracellular matrix (ECM), a key component of the microenvironment shapes the response of melanoma cells to therapies targeting the BRAFV600 oncogenic pathway and melanoma progression. I will first present an overview of our recent findings showing that BRAF-targeted therapies induce a fibrotic-like response associated with melanoma phenotypic plasticity, ECM remodeling, and tumor stiffening. I will also present data showing how we can therapeutically manipulate tumor-associated fibrosis and ECM-mediated signaling to overcome therapy resistance and delay tumor relapse. Finally, I will present new data implicating a role for DDR collagen receptors in mechanotransduction, and demonstrating that mechanical addiction of the dedifferentiated melanoma cell state represents a new vulnerability for this aggressive phenotype.

Selected publications

• Tichet et al. Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis Nat Commun 2015
• Rathore et al. Cancer cell-derived long pentraxin 3 (PTX3) promotes melanoma migration through a toll-like receptor 4 (TLR4)/NF-κB signaling pathway Oncogene 2019
• Girard et al. A Feed-Forward Mechanosignaling Loop Confers Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutant Melanoma Cancer Res 2020
• Diazzi et al. Blockade of the pro-fibrotic reaction mediated by the miR-143/-145 cluster enhances the responses to targeted therapy in melanoma EMBO Mol Med 2022
• Berestjuk et al. Targeting Discoidin Domain Receptors DDR1 and DDR2 overcomes matrix-mediated tumor cell adaptation and tolerance to BRAF-targeted therapy in melanoma EMBO Mol Med 2022
• Popovic & Tartare-Deckert. Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance Front Oncol 2022
• Rovera et al. Secretion of IL1 by Dedifferentiated Melanoma Cells Inhibits JAK1-STAT3-Driven Actomyosin Contractility of Lymph Node Fibroblastic Reticular Cells Cancer Res 2022
• Diazzi et al. The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance Oncogenesis 2023