Plakophilin 1 is methylated and has a tumor suppressive activity in human lung cancer.
DNA methylation
Lung cancer
Plakophilin 1
Tissue microarray
Tumor suppressor
Journal
Experimental and molecular pathology
ISSN: 1096-0945
Titre abrégé: Exp Mol Pathol
Pays: Netherlands
ID NLM: 0370711
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
13
03
2019
revised:
28
03
2019
accepted:
01
04
2019
pubmed:
5
4
2019
medline:
26
2
2020
entrez:
5
4
2019
Statut:
ppublish
Résumé
Plakophilin 1 (PKP1) is an important plaque component of desmosomes, major intercellular adhesive junctions that act as anchorage points for intermediate filaments. Abnormal expression of PKP1 was observed in various types of cancer, however so far its function in lung cancer has not yet been elucidated. The expression of PKP1 was analyzed by RT-PCR and western blotting in lung cancer cell lines. The protein expression of PKP1 was evaluated by immunohistochemistry in tissue microarray. The epigenetic mechanism of PKP1 was explored by demethylation test, bisulfite sequencing and Methylation-Specific-PCR. The function of PKP1 was investigated by stable transfection with an expression vector. We found that PKP1 was downregulated in 6 out of 8 lung cancer cell lines, and downregulation of PKP1 was associated with DNA hypermethylation. In advanced primary lung tumor samples, higher expression of PKP1 was significantly associated with favorable clinical outcome (p = .003). Ectopic expression of PKP1 inhibited cell proliferation, colony formation, migration/invasion and enhanced apoptosis. These phenomena are accompanied by increased caspase 3/7 activities and cleaved PARP-1 as well as decreased extracellular signal-regulated kinase (ERK) activity. Taken together, our data suggest that PKP1 is a novel tumor suppressor and its protein expression might be a potential prognostic marker for patients with advanced lung cancer.
Sections du résumé
BACKGROUND
Plakophilin 1 (PKP1) is an important plaque component of desmosomes, major intercellular adhesive junctions that act as anchorage points for intermediate filaments. Abnormal expression of PKP1 was observed in various types of cancer, however so far its function in lung cancer has not yet been elucidated.
METHODS
The expression of PKP1 was analyzed by RT-PCR and western blotting in lung cancer cell lines. The protein expression of PKP1 was evaluated by immunohistochemistry in tissue microarray. The epigenetic mechanism of PKP1 was explored by demethylation test, bisulfite sequencing and Methylation-Specific-PCR. The function of PKP1 was investigated by stable transfection with an expression vector.
RESULTS
We found that PKP1 was downregulated in 6 out of 8 lung cancer cell lines, and downregulation of PKP1 was associated with DNA hypermethylation. In advanced primary lung tumor samples, higher expression of PKP1 was significantly associated with favorable clinical outcome (p = .003). Ectopic expression of PKP1 inhibited cell proliferation, colony formation, migration/invasion and enhanced apoptosis. These phenomena are accompanied by increased caspase 3/7 activities and cleaved PARP-1 as well as decreased extracellular signal-regulated kinase (ERK) activity.
CONCLUSION
Taken together, our data suggest that PKP1 is a novel tumor suppressor and its protein expression might be a potential prognostic marker for patients with advanced lung cancer.
Identifiants
pubmed: 30946843
pii: S0014-4800(19)30191-1
doi: 10.1016/j.yexmp.2019.04.001
pii:
doi:
Substances chimiques
PKP1 protein, human
0
Plakophilins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
73-79Informations de copyright
Copyright © 2019. Published by Elsevier Inc.