Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Cell Rep ; 25(7): 1841-1855.e5, 2018 11 13.
Article in English | MEDLINE | ID: mdl-30428352

ABSTRACT

Signal transduction pathways stimulated by secreted growth factors are tightly regulated at multiple levels between the cell surface and the nucleus. The trafficking of cell surface receptors is emerging as a key step for regulating appropriate cellular responses, with perturbations in this process contributing to human diseases, including cancer. For receptors recognizing ligands of the transforming growth factor ß (TGF-ß) family, little is known about how trafficking is regulated or how this shapes signaling dynamics. Here, using whole genome small interfering RNA (siRNA) screens, we have identified the ESCRT (endosomal sorting complex required for transport) machinery as a crucial determinant of signal duration. Downregulation of ESCRT components increases the outputs of TGF-ß signaling and sensitizes cells to low doses of ligand in their microenvironment. This sensitization drives an epithelial-to-mesenchymal transition (EMT) in response to low doses of ligand, and we demonstrate a link between downregulation of the ESCRT machinery and cancer survival.


Subject(s)
Endosomal Sorting Complexes Required for Transport/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Activins/metabolism , Animals , Bone Morphogenetic Proteins/metabolism , Cell Line , Down-Regulation , Epithelial-Mesenchymal Transition , Genome, Human , Humans , Lysosomes/metabolism , Mice , Multivesicular Bodies/metabolism , Neoplasms/pathology , Phosphorylation , Prognosis , Protein Transport , Proteolysis , Smad2 Protein/metabolism , Survival Analysis , Ubiquitin-Protein Ligases/metabolism , Up-Regulation
SELECTION OF CITATIONS
SEARCH DETAIL
...