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Last name: OHANNA
First name: Mickaël
International audience
No abstract available
Microphthalmia-associated transcription factor (MITF) was initially shown to play a key role in melanocyte differentiation through the direct transcriptional control of TYROSINASE, TYRP1 and DCT genes, encoding the three enzymes involved in melanin synthesis or melanogenesis. Sixteen years after the first description of MITF, more than 40...
Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence. However, recent...
In BRAFV600E melanoma cells, a global metabolomic analysis discloses a decrease in nicotinamide adenine dinucleotide (NAD+) levels upon PLX4032 treatment that is conveyed by a STAT5 inhibition and a transcriptional regulation of the nicotinamide phosphoribosyltransferase (NAMPT) gene. NAMPT inhibition decreases melanoma cell proliferation both...
Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a...
Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a...
SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the cell context. Whether SIRT1 plays a role in melanoma biology remained poorly elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma cell proliferation. SIRT1 suppression by genetic or pharmacological approaches induces cell cycle arrest and...
Metastatic melanoma is a deadly skin cancer and is resistant to almost all existing treatment. Vemurafenib, which targets the BRAFV600E mutation, is one of the drugs that improves patient outcome, but the patients next develop secondary resistance and a return to cancer. Thus, new therapeutic strategies are needed to treat melanomas and to...
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...
Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated...
Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with...
International audience
International audience
Extracellular vesicles (EVs) have been shown to play an important role in intercellular communication as carriers of DNA, RNA and proteins. While the intercellular transfer of miRNA through EVs has been extensively studied, the stability of extracellular miRNA (ex-miRNA) once engulfed by a recipient cell remains to be determined. Here, we...
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and...
Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated...
BACKGROUND:MITF encodes an oncogenic lineage-specific transcription factor in which a germline mutation ( MITFE318K ) was identified in human patients predisposed to both nevus formation and, among other tumor types, melanoma. The molecular mechanisms underlying the oncogenic activity of MITF E318K remained uncharacterized.METHODS:Here, we...