Exon-based clustering of murine breast tumor transcriptomes reveals alternative exons whose expression is associated with metastasis

In the field of bioinformatics, exon profiling is a developing area of disease-associated transcriptome analysis. In this study, we performed a microarray-based transcriptome analysis at the single exon level in mouse 4T1 primary mammary tumors with different metastatic capabilities. A novel bioinformatics platform was developed that identified 679 genes with differentially expressed exons in 4T1 tumors, many of which were involved in cell morphology and movement. Of 152 alternative exons tested by reverse transcription-PCR, 97 were validated as differentially expressed in primary tumors with different metastatic capability. This analysis revealed candidate progression genes, hinting at variations in protein functions by alternate exon usage. In a parallel effort, we developed a novel exon-based clustering analysis and identified alternative exons in tumor transcriptomes that were associated with dissemination of primary tumor cells to sites of pulmonary metastasis. This analysis also revealed that the splicing events identified by comparing primary tumors were not aberrant events. Lastly, we found that a subset of differentially spliced variant transcripts identified in the murine model was associated with poor prognosis in a large clinical cohort of patients with breast cancer. Our findings illustrate the utility of exon profiling to define novel theranostic markers for study in cancer progression and metastasis

Exon-based clustering of murine breast tumor transcriptomes reveals alternative exons whose expression is associated with metastasis

In the field of bioinformatics, exon profiling is a developing area of disease-associated transcriptome analysis. In this study, we performed a microarray-based transcriptome analysis at the single exon level in mouse 4T1 primary mammary tumors with different metastatic capabilities. A novel bioinformatics platform was developed that identified 679 genes with differentially expressed exons in 4T1 tumors, many of which were involved in cell morphology and movement. Of 152 alternative exons tested by reverse transcription-PCR, 97 were validated as differentially expressed in primary tumors with different metastatic capability. This analysis revealed candidate progression genes, hinting at variations in protein functions by alternate exon usage. In a parallel effort, we developed a novel exon-based clustering analysis and identified alternative exons in tumor transcriptomes that were associated with dissemination of primary tumor cells to sites of pulmonary metastasis. This analysis also revealed that the splicing events identified by comparing primary tumors were not aberrant events. Lastly, we found that a subset of differentially spliced variant transcripts identified in the murine model was associated with poor prognosis in a large clinical cohort of patients with breast cancer. Our findings illustrate the utility of exon profiling to define novel theranostic markers for study in cancer progression and metastasis

Tester une innovation technique favorable aux abeilles mellifères par des approches participative et expérimentale – Projet InterAPI 1

La combinaison de la mortalité et de colonies non productrices en sortie d’hiver est responsable d’un taux de mortalité représentant près d’un tiers du cheptel. Nous nous sommes intéressés aux conditions environnementales des colonies d’abeilles mellifères à cette période cruciale de pré-hivernage. Une solution technique spécifique a été testée pour étudier l’influence de l’environnement sur la période d’hivernage des colonies. C’est grâce à une double approche d’accompagnement des acteurs et expérimentale s’appuyant sur une implication forte des agriculteurs et apiculteurs de la Beauce, que les partenaires du projet InterAPI mettent en évidence l’intérêt d’un aménagement du territoire qui intègre des cultures intermédiaires mellifères (CIM) favorables aux colonies. Ils identifient les espèces candidates et leurs caractéristiques grâce à deux outils d’aide à la gestion de cette interculture.The rates of honeybee colony winter losses remain very high describing mortalities and non-producing colonies after wintering represents nearly a third of the producing colonies. We were interested in environmental conditions of honeybee colonies at this crucial time. A technical solution has been tested and specifically to study environment influence on the wintering period of the colonies. Through a dual approach of co-construction and experimental, based on a strong involvement of farmers and beekeepers in Beauce region, partners of InterAPI project highlight the interest of a landscape management which includes melliferous catch crops. They identify candidate species and their characteristics using two tools helping the management of catch crops

The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death

International audienceEctodysplasin receptor EDAR is seen as a typical Tumor Necrosis Factor receptor (TNFR) family member known to interact with its ligand Eda-A1, and signaling mainly through the nuclear factor-kappaB (NF-κB) and c-jun N-terminal kinases pathways. Mutations in genes that encode proteins involved in EDAR transduction cascade cause anhidrotic ectodermal dysplasia. Here, we report an unexpected pro-apoptotic activity of EDAR when unbound to its ligand Eda-A1, which is independent of NF-κB pathway. Contrarily to other death receptors, EDAR does recruit caspase-8 to trigger apoptosis but solely upon ligand withdrawal, thereby behaving as the so-called dependence receptors. We propose that pro-apoptotic activity of unbound EDAR confers it a tumor suppressive activity. Along this line, we identified loss-of-pro-apoptotic function mutations in EDAR gene in human melanoma. Moreover, we show that the invalidation of EDAR in mice promotes melanoma progression in a B-Raf mutant background. Together, these data support the view that EDAR constrains melanoma progression by acting as a dependence receptor