Depletion of slow-cycling PDGFRαADAM12 mesenchymal cells promotes antitumor immunity by restricting macrophage efferocytosis.

The capacity to survive and thrive in conditions of limited resources and high inflammation is a major driver of tumor malignancy. Here we identified slow-cycling ADAM12PDGFRα mesenchymal stromal cells (MSCs) induced at the tumor margins in mouse models of melanoma, pancreatic cancer and prostate cancer. Using inducible lineage tracing and transcriptomics, we demonstrated that metabolically altered ADAM12 MSCs induced pathological angiogenesis and immunosuppression by promoting macrophage efferocytosis and polarization through overexpression of genes such as Gas6, Lgals3 and Csf1.

The clinical phenotype of germline RUNX1 mutations in relation to the accompanying somatic variants and RUNX1 isoform expression.

Germline RUNX1 mutations lead to familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, abnormal bleeding, and an elevated risk of developing myelodysplastic neoplasia (MDS) and acute myeloid leukemia (AML) at young age. However, it is not known why or how germline carriers of RUNX1 mutations have a particular propensity to develop myeloid hematologic malignancies, but the acquisition and composition of somatic mutations are believed to initiate and determine disease progression. We present a novel family pedigree that shares a common germline RUNX1 variant and exhibits a spectrum of somatic mutations and related myeloid malignancies (MM).

Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors.

Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context.

The Mitochondrial PHB Complex Determines Lipid Composition and Interacts With the Endoplasmic Reticulum to Regulate Ageing.

Metabolic disorders are frequently associated with physiological changes that occur during ageing. The mitochondrial prohibitin complex (PHB) is an evolutionary conserved context-dependent modulator of longevity, which has been linked to alterations in lipid metabolism but which biochemical function remains elusive. In this work we aimed at elucidating the molecular mechanism by which depletion of mitochondrial PHB shortens the lifespan of wild type animals while it extends that of insulin signaling receptor () mutants.

β-catenin-activated hepatocellular carcinomas are addicted to fatty acids.

Objectives: -mutated hepatocellular carcinomas (HCCs) constitute a major part of human HCC and are largely inaccessible to target therapy. Yet, little is known about the metabolic reprogramming induced by β-catenin oncogenic activation in the liver. We aimed to decipher such reprogramming and assess whether it may represent a new avenue for targeted therapy of -mutated HCC.