Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis.

Functional and structural analysis of cytokine-selective IL6ST defects that cause recessive hyper-IgE syndrome.

Background: Biallelic variants in IL6ST, encoding GP130, cause a recessive form of hyper-IgE syndrome (HIES) characterized by high IgE level, eosinophilia, defective acute phase response, susceptibility to bacterial infections, and skeletal abnormalities due to cytokine-selective loss of function in GP130, with defective IL-6 and IL-11 and variable oncostatin M (OSM) and IL-27 levels but sparing leukemia inhibitory factor (LIF) signaling.

Objective: Our aim was to understand the functional and structural impact of recessive HIES-associated IL6ST variants.

Methods: We investigated a patient with HIES by using exome, genome, and RNA sequencing.

A variant in with a selective IL-11 signaling defect in human and mouse.

The GP130 cytokine receptor subunit encoded by is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in (p.R281Q) in a patient with craniosynostosis and retained deciduous teeth.