TARTARE-DECKERT , Sophie

Current treatments for metastatic cutaneous melanoma include immunotherapies and drugs targeting key molecules of the mitogen-activated protein kinase (MAPK) pathway, which is often activated by BRAF driver mutations. Overall responses from patients with metastatic BRAF mutant melanoma are better with therapies combining BRAF and...

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The extracellular matrix (ECM) is critical for maintaining tissue homeostasis therefore its production, assembly and mechanical stiffness are highly regulated in normal tissues. However, in solid tumors, increased stiffness resulting from abnormal ECM structural changes is associated with disease progression, an increased risk of metastasis and...

Actin networks are dynamically regulated through constant depolymerization and polymerization cycles. Although the fundamental mechanisms that govern these processes have been identified, the nature and role of post-translational modifications (PTMs) of actin and actin regulatory proteins are not completely understood. Here, we employed Actin...

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Advanced cutaneous melanoma is one of the most challenging cancers to treat because of its high plasticity, metastatic potential, and resistance to treatment. New targeted therapies and immunotherapies have shown remarkable clinical efficacy. However, such treatments are limited to a subset of patients and relapses often occur, warranting...

Post-translational modification by ubiquitin is crucial for protein turnover. Deubiquitinases (DUBs) remove ubiquitin chains from target proteins to prevent their degradation by the proteasome, thus acting as gatekeepers of protein homeostasis alongside the ubiquitin-proteasome system (UPS). Tumor cells exhibit remarkable plasticity, enabling...

Cladribine is an oral synthetic purine analog that depletes lymphocytes and induces a dose-dependent reduction of T and B cells. It was approved for the therapy of highly active relapsing-remitting multiple sclerosis. Given cladribine's mechanism of action, an increased risk of malignancies was suspected from the number of cancers that occurred...

Loss of tumor-suppressive pathways that control cellular senescence is a crucial step in malignant transformation. Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase that has been recently implicated in tumor suppression of melanoma, a deadly skin cancer derived from pigment-producing melanocytes. However, the mechanism by which Syk...

We have previously demonstrated that the thiazolidinedione ciglitazone inhibited, independently of PPAR activation, melanoma cell growth. Further investigations now show that ciglitazone effects are mediated through the regulation of secreted factors. Q-PCR screening of several genes involved in melanoma biology reveals that ciglitazone...

Abstract Fibroblastic reticular cells (FRC) are immunologically specialized fibroblasts controlling the size and microarchitecture of the lymph node (LN), partly through their contractile properties. Swelling is a hallmark of tumor-draining LN in lymphophilic cancers such as cutaneous melanoma, a very aggressive and heterogeneous tumor with...

Abstract Extracellular matrix (ECM) stiffening, resulting from increased collagen deposition and cross-linking, is a key biophysical factor of the tumor microenvironment. Cutaneous melanoma is a deadly metastatic cancer. Its aggressiveness stems from high intratumoral heterogeneity, resulting from the plasticity of melanoma cells, which transit...

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Resistance to BRAF and MEK inhibitors in BRAF V600E mutant melanomas remains a major obstacle that limits patient benefit. Microenvironment components including the extracellular matrix (ECM) can support tumor cell adaptation and tolerance to targeted therapies, however the underlying mechanisms remain poorly understood. Here, we investigated...