Matrix metalloproteinase-9 cooperates with transcription factor Snail to induce epithelial-mesenchymal transition

Autor: Pei Hsun Tsai, Chun Yu Lin, Ping Ping Lee, Chang Jen Huang, Ming Ting Lee, Chithan C. Kandaswami, Jiuan Jiuan Hwang
Rok vydání: 2011
Předmět:
Cancer Research
Epithelial-Mesenchymal Transition
Blotting
Western
Fluorescent Antibody Technique
Motility
Vimentin
macromolecular substances
Snail
Matrix Metalloproteinase Inhibitors
Matrix metalloproteinase
Cell Movement
biology.animal
Biomarkers
Tumor
Tumor Cells
Cultured
Humans
RNA
Messenger
Epithelial–mesenchymal transition
RNA
Small Interfering
skin and connective tissue diseases
Transcription factor
Oligonucleotide Array Sequence Analysis
Wound Healing
biology
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
General Medicine
Cadherins
Cell biology
Gene Expression Regulation
Neoplastic
Fibronectin
Matrix Metalloproteinase 9
Oncology
Carcinoma
Squamous Cell
biology.protein
Snail Family Transcription Factors
A431 cells
hormones
hormone substitutes
and hormone antagonists
Transcription Factors
Zdroj: Cancer Science. 102:815-827
ISSN: 1347-9032
Popis: One of the most fundamental biological processes in tumor metastasis is the process of epithelial–mesenchymal transition (EMT). During EMT, zinc-finger-family of transcription factors such as Snail, Slug and Twist, and matrix metalloproteinases (MMPs) are upregulated, and this correlates with increased tumor cell invasion and motility. We previously obtained a highly invasive A431-III tumor subline, which is a rich source of MMP-9 and observed a plausible link between MMP levels and the promotion of EMT. To gain further understanding of EMT, we investigated the contribution of distinct MMPs to the induction of EMT. Exposing A431, cervical carcinoma parental cells, to MMP-9 stimulated a phenotypic alteration and cells became spindle-like as shown for A431-III cells. In the present communication, we document changes in gene expression profiles of A431-P and A431-III cells, including those of genes involved in cell adhesion, cytoskeleton reorganization, polarity, migration and transcription. Treatment of both A431-P and A431-III cells with GM6001, a broad spectrum MMP inhibitor, resulted in the diminution of vimentin and fibronectin, indicating a role for MMP-9 in the induction of EMT. Abrogation of MMP-9-mediated cell–cell contact in both A431-P and A431-III cells using MMP-9 siRNA resulted in decreased cell invasion, motility and altered cytoskeleton arrangement together with a reduction in Snail expression. Knockdown of Snail resulted in similar changes along with diminished MMP-9 expression. These data suggest a higher capacity of MMP-9 than that of Snail in eliciting the development of EMT in A431 cells. Based on these findings, we speculate that the overexpression of MMP-9 in A431-III cells might directly induce (or stimulate) EMT and that the transcriptional factor, Snail, could cooperatively engage in this phenomenon. (Cancer Sci 2011; 102: 815–827)
Databáze: OpenAIRE
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