Extracellular Remodelling During Oncogenic Ras-Induced Epithelial-Mesenchymal Transition Facilitates MDCK Cell Migration
Details
Publication Year 2010-02, Volume 9, Issue #2, Page 1007-1019
Journal Title
JOURNAL OF PROTEOME RESEARCH
Publication Type
Journal Article
Abstract
Epithelial-mesenchymal transition (EMT) describes a process whereby immotile epithelial cells escape structural constraints imposed by cellular architecture and acquire a phenotype characteristic of migratory mesenchymal cells. Implicated in carcinoma progression and metastasis, EMT has been the focus of several recent proteomics-based studies aimed at identifying new molecular players. To gain insights into extracellular mediators associated with EMT, we conducted an extensive proteomic analysis of the secretome from MDCK cells following oncogenic Ras-induced EMT (21D1 cells). Using Orbitrap technology and a label-free quantitative approach, differential expression of several secreted modulators were revealed. Proteomic findings were further substantiated by mRNA transcript expression analysis with 71% concordance. MDCK cells undergoing Ras-induced EMT remodel the extracellular matrix (ECM) via diminished expression of basement membrane constituents (Collagen type IV and laminin 5), up-regulation of extracellular proteases (MMP-1, kallikreins -6 and -7), and increased production and secretion of ECM constituents (SPARC, Collagen type 1, fibulins -1 and -3, biglycan, and decorin). Collectively, these findings suggest that hierarchical regulation of a subset of extracellular effectors may coordinate a biological response during EMT that enhances cell motility. Transient silencing of MMP-1 in 21D1 cells via siRNA-mediated knockdown attenuated cell migration. Many of the secretome proteins identified broaden our understanding of the EMT process.
Publisher
AMER CHEMICAL SOC
Keywords
E-CADHERIN EXPRESSION; TRANSCRIPTION FACTOR; SHOTGUN PROTEOMICS; MASS-SPECTROMETER; PROSTATE-CANCER; TUMOR MICROENVIRONMENT; MATRICELLULAR PROTEIN; BASEMENT-MEMBRANE; LAMININ ISOFORMS; CARCINOMA CELLS
Publisher's Version
https://doi.org/10.1021/pr900907g
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2010-02-01 12:00:00
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙