Abstract
Plakophilin3 (PKP3) loss results in increased transformation in multiple cell lines in vitro and increased tumor formation in vivo. A microarray analysis performed in the PKP3 knockdown clones, identified an inflammation associated gene signature in cell lines derived from stratified epithelia as opposed to cell lines derived from simple epithelia. However, in contrast to the inflammation associated gene signature, the expression of MMP7 was increased upon PKP3 knockdown in all the cell lines tested. Using vector driven RNA interference, it was demonstrated that MMP7 was required for in-vitro cell migration and invasion and tumor formation in vivo. The increase in MMP7 levels was due to the increase in levels of the Phosphatase of Regenerating Liver3 (PRL3), which is observed upon PKP3 loss. The results suggest that MMP7 over-expression may be one of the mechanisms by which PKP3 loss leads to increased cell invasion and tumor formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinogenesis / metabolism*
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Carcinogenesis / pathology*
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Cell Line
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Cell Transformation, Neoplastic
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Clone Cells
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Epithelium / pathology
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Gene Knockdown Techniques
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Humans
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Inflammation / pathology
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Matrix Metalloproteinase 7 / metabolism*
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Invasiveness
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Neoplasm Proteins / metabolism
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Plakophilins / metabolism*
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Protein Tyrosine Phosphatases / metabolism
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Transcriptome / genetics
Substances
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Neoplasm Proteins
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PKP3 protein, human
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Plakophilins
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PTP4A3 protein, human
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Protein Tyrosine Phosphatases
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Matrix Metalloproteinase 7
Grants and funding
This work was supported by a grant from the Department of Science and Technology (DST), Government of India to SND. The grant number is SR/SO/HS-011/2009. The work was also supported by intra-mural funds from ACTREC. SB was supported by a fellowship from the Council for Scientific and Industrial Research (CSIR) Govt. of India. The fellowship number is 09/513(0074)/2009-EMR-I. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.