Krüppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role in somatic stem cells is unknown. Here we show that Krüppel-like factor 5-deficient haematopoietic stem cells and progenitors fail to engraft after transplantation. This haematopoietic stem cell and progenitor defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, ...

Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. H...

BACKGROUND TGF-β1 controls many pathophysiological processes including tissue homeostasis, fibrosis, and cancer progression. Together with its latency-associated peptide (LAP), TGF-β1 binds to the latent TGF-β1-binding protein-1 (LTBP-1), which is part of the extracellular matrix (ECM). Transmission of cell force via integrins is one major mechanism to activate latent TGF-β1 from ECM stores. La...

The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates with β1 integrins to control cell-matrix interactions. Here, we investigated whether LASV binding to DG triggers signal transduction, mimicking the natural ligan...

Fundamental to an improvement of cancer cure rates is a better understanding of the underlying molecular mechanisms driving resistance to standard treatments such as radioand chemotherapy. A powerful and promising approach to sensitize cancer cells to therapy is represented by Paul Ehrlich ́s old and still up-to-date concept of the “magic bullet”. Reviewing the complexity of the “hallmarks of ca...

αν and β1 integrins mediate Aβ-induced neurotoxicity in primary hippocampal neurons. We treated hippocampal neurons with 2.5 µg/mL 17E6 and 5 µg/mL ab58524, which are specific αν and β1 integrin antagonists, respectively, for 42 h prior to 10 µM Aβ treatment. Next, we employed small interfering RNA (siRNA) to silence focal adhesion kinase (FAK), a downstream target gene of integrins. The siRNAs...

Background: Integrins are transmembrane mechanosensitive proteins that negatively contribute to the pathogenesis of different types chronic liver disease and can activate focal adhesion kinase (FAK). Objectives: This study aimed determine hepatic integrin β1 FAK mRNA as well transcriptional coactivator with PDZ-binding motif (TAZ) protein expressions in cirrhotic patients simple steatosis. Meth...

Memory consolidation theory posits that newly acquired information passes through a series of stabilization steps before being firmly encoded. We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. Quantita...

C ompetition for the cytoplasmic tail of an integrin allows cells to read different matrix densities, say Millon-Frémillon et al. The tail region of β1 integrin is tiny—only 47 amino acids long. That doesn’t leave much room for the binding of cytoplasmic accessory proteins that help control the integrin’s activation state. When talin holds this position, it fl ips open integrin as a fi rst step...