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Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in prostate cancer cells.

ABSTRACT: Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which the epithelial cells downregulate cell-cell adhesion genes such as E-Cadherin and upregulate mesenchymal genes such as vimentin, leading to increased invasion and migration. Very little is known about the role of Snail in cellular adhesion to the extracellular matrix. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen I matrix through integrin regulation, concomitant with increased cell migration. Androgen-independent C4-2 cells, an aggressive subline of androgen-dependent LNCaP cells, exhibited decreased cell adhesion and increased cell migration on fibronectin and collagen I as compared to LNCaP cells, which was reversed by Snail knock down in C4-2 cells. ARCaP and LNCaP prostate cancer cells stably transfected with Snail displayed decreased adhesion and increased cell migration on fibronectin and collagen I as compared to control Neo-transfected cells, which was reversed by Snail knockdown. Flow cytometry analysis revealed a decrease in a5, a2 and b1 integrin expression in ARCaP Snail-transfected cells that was reversed in Snail knock down cells. We also observed an increase in ERK phosphorylation in ARCaP Snail-transfected cells as compared to control ARCaP-Neo cells, and inhibition of the MAPK pathway with UO126 inhibitor in ARCaP Snail-transfected cells abrogated Snail-mediated decrease in cell adhesion and reinduced a5, a2 and b1 integrin expression. Collectively, these studies define a new role for Snail transcription factor in cell adhesion to the ECM, which may be mediated by MAPK signaling, and may be crucial for cell detachment and subsequent metastasis.

SUBMITTER: Neal CL

PROVIDER: S-EPMC3210209 | biostudies-literature | 2011 May-Jun

REPOSITORIES: biostudies-literature

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Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in prostate cancer cells.

Neal Corey L CL Mckeithen Danielle D Odero-Marah Valerie A VA

Cell adhesion & migration 20110501 3

Snail transcription factor induces epithelial-mesenchymal transition (EMT) in which the epithelial cells downregulate cell-cell adhesion genes such as E-Cadherin and upregulate mesenchymal genes such as vimentin, leading to increased invasion and migration. Very little is known about the role of Snail in cellular adhesion to the extracellular matrix. We hypothesized that Snail will lead to decreased cellular adhesion to fibronectin and collagen I matrix through integrin regulation, concomitant w ...[more]

PMID: 21478672

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Project description:BackgroundThe hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration.MethodsWe evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting.ResultsWe demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin.ConclusionsWe demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving the migration of donor cells within the host tissue, a main issue regarding this approach.

Dataset Information

Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in prostate cancer cells.

Publications

Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in prostate cancer cells.

Similar Datasets

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