ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion
| العنوان: | ß1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft signalsome driving invadopodia activity and invasion |
|---|---|
| المؤلفون: | Francesca Di Sole, MariaLuisa L. Carcangiu, Loredana Moro, Ester Antelmi, Rosa Rubino, Nicola Antonio Martino, Stephan J. Reshkin, Valeria Casavola, Rosa Angela Cardone, Maria Raffaella Greco |
| المصدر: | PLoS ONE, Vol 8, Iss 9, p e75113 (2013) PLoS ONE PloS one 8 (2013). doi:10.1371/journal.pone.0075113 info:cnr-pdr/source/autori:Antelmi E.; Cardone R.A.; Greco M.R.; Rubino R.; Di Sole F.; Martino N.A.; Casavola V.; Carcangiu M.L.; Moro L.; Reshkin S.J./titolo:ß1 Integrin Binding Phosphorylates Ezrin at T567 to Activate a Lipid Raft Signalsome Driving Invadopodia Activity and Invasion/doi:10.1371%2Fjournal.pone.0075113/rivista:PloS one/anno:2013/pagina_da:/pagina_a:/intervallo_pagine:/volume:8 |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | genetic structures, Receptor, ErbB-2, Science, Integrin, Fluorescent Antibody Technique, Breast Neoplasms, macromolecular substances, Biology, environment and public health, Ezrin, Membrane Microdomains, Image Processing, Computer-Assisted, Humans, Immunoprecipitation, Neoplasm Invasiveness, Pseudopodia, Phosphorylation, Cytoskeleton, Lipid raft, Integrin binding, DNA Primers, Analysis of Variance, Multidisciplinary, Integrin beta1, Actin cytoskeleton, Immunohistochemistry, Cell biology, Extracellular Matrix, Cytoskeletal Proteins, Gene Expression Regulation, Italy, Invadopodia, biology.protein, Medicine, Female, Signal Transduction, Research Article |
| الوصف: | Extracellular matrix (ECM) degradation is a critical process in tumor cell invasion and requires matrix degrading protrusions called invadopodia. The Na(+)/H(+) exchanger (NHE1) has recently been shown to be fundamental in the regulation of invadopodia actin cytoskeleton dynamics and activity. However, the structural link between the invadopodia cytoskeleton and NHE1 is still unknown. A candidate could be ezrin, a linker between the NHE1 and the actin cytoskeleton known to play a pivotal role in invasion and metastasis. However, the mechanistic basis for its role remains unknown. Here, we demonstrate that ezrin phosphorylated at T567 is highly overexpressed in the membrane of human breast tumors and positively associated with invasive growth and HER2 overexpression. Further, in the metastatic cell line, MDA-MB-231, p-ezrin was almost exclusively expressed in invadopodia lipid rafts where it co-localized in a functional complex with NHE1, EGFR, ß1-integrin and phosphorylated-NHERF1. Manipulation by mutation of ezrins T567 phosphorylation state and/or PIP2 binding capacity or of NHE1s binding to ezrin or PIP2 demonstrated that p-ezrin expression and binding to PIP2 are required for invadopodia-mediated ECM degradation and invasion and identified NHE1 as the membrane protein that p-ezrin regulates to induce invadopodia formation and activity. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2843d7676dd6a3d43b50167e1a18340cTest https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086451/?tool=EBITest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2843d7676dd6a3d43b50167e1a18340c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|