MMP7 is required to mediate cell invasion and tumor formation upon Plakophilin3 loss

Srikanta Basu; Rahul Thorat; Sorab N Dalal

doi:10.1371/journal.pone.0123979

MMP7 is required to mediate cell invasion and tumor formation upon Plakophilin3 loss

PLoS One. 2015 Apr 13;10(4):e0123979. doi: 10.1371/journal.pone.0123979. eCollection 2015.

Authors

Srikanta Basu¹, Rahul Thorat¹, Sorab N Dalal¹

Affiliation

¹ Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India.

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

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinogenesis / metabolism*
Carcinogenesis / pathology*
Cell Line
Cell Transformation, Neoplastic
Clone Cells
Epithelium / pathology
Gene Knockdown Techniques
Humans
Inflammation / pathology
Matrix Metalloproteinase 7 / metabolism*
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Plakophilins / metabolism*
Protein Tyrosine Phosphatases / metabolism
Transcriptome / genetics

Substances

Neoplasm Proteins
PKP3 protein, human
Plakophilins
PTP4A3 protein, human
Protein Tyrosine Phosphatases
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.