SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined by a progressive decline in lung function due to scarring and accumulation of extracellular matrix (ECM) proteins. The SOCS (Suppressor Of Cytokine Signaling) domain is a 40 amino acid conserved domain known to form a functional ubiquitin ligase complex targeting the Von Hippel Lindau (VHL) protein for proteasomal degradation. Here we show that the SOCS conserved domain operates as a molecular tool, to disrupt collagen and fibronectin fibrils in the ECM associated with fibrotic lung myofibroblasts.

Hypoxia-inducible factor-1 alpha expression is induced by IL-2 via the PI3K/mTOR pathway in hypoxic NK cells and supports effector functions in NKL cells and ex vivo expanded NK cells.

Natural killer (NK) cells are cytotoxic innate lymphocytes that are specialized to kill tumor cells. NK cells are responsive to the primary cytokine IL-2 in the tumor microenvironment (TME), to activate its effector functions against tumors. Despite their inherent ability to kill tumor cells, dysfunctional NK cells observed within advanced solid tumors are associated with poor patient survival.

Fibronectin assembly regulates lumen formation in breast acini.

Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that self-assembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial-to-mesenchymal transition. The role of the FN matrix of epithelial cells in driving such processes remains less well understood and is the focus of this study.

HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl.

Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined.

Deoxycholate Fractionation of Fibronectin (FN) and Biotinylation Assay to Measure Recycled FN Fibrils in Epithelial Cells.

Fibronectin (FN) is an extracellular matrix protein that is secreted by many cell types and binds predominantly to the cell surface receptor Integrin α5β1. Integrin α5β1 binding initiates the step-wise assembly of FN into fibrils, a process called fibrillogenesis. We and several others have demonstrated critical effects of fibrillogenesis on cell migration and metastasis.