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Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination

Expression of the gene for protein‐arginine deiminase 2 (PADI2) has been shown to be downregulated in colon cancer, with such downregulation being indicative of a poor prognosis in individuals with this disease. We have now examined the expression of PADI2 in matched colon cancer and normal colon ti...

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Autores principales: Funayama, Ryo, Taniguchi, Hajime, Mizuma, Masamichi, Fujishima, Fumiyoshi, Kobayashi, Minoru, Ohnuma, Shinobu, Unno, Michiaki, Nakayama, Keiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406534/
https://www.ncbi.nlm.nih.gov/pubmed/28403548
http://dx.doi.org/10.1111/cas.13179
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author Funayama, Ryo
Taniguchi, Hajime
Mizuma, Masamichi
Fujishima, Fumiyoshi
Kobayashi, Minoru
Ohnuma, Shinobu
Unno, Michiaki
Nakayama, Keiko
author_facet Funayama, Ryo
Taniguchi, Hajime
Mizuma, Masamichi
Fujishima, Fumiyoshi
Kobayashi, Minoru
Ohnuma, Shinobu
Unno, Michiaki
Nakayama, Keiko
author_sort Funayama, Ryo
collection PubMed
description Expression of the gene for protein‐arginine deiminase 2 (PADI2) has been shown to be downregulated in colon cancer, with such downregulation being indicative of a poor prognosis in individuals with this disease. We have now examined the expression of PADI2 in matched colon cancer and normal colon tissue specimens as well as in colon cancer cell lines. We found that isoform 1 of PADI2 is the predominant isoform in colon tissue and is downregulated during colon carcinogenesis. Immunohistochemical analysis showed that PADI2 is expressed in normal colonic epithelial cells. Overexpression of PADI2 isoform 1 suppressed the proliferation of colon cancer cells in vitro in association with increased protein citrullination. Expression of a catalytically inactive mutant (C647A) of PADI2 or of PADI2 isoform 2 did not induce such effects, indicating that the protein citrullination activity of PADI2 is required for inhibition of cell growth. The growth defect induced by PADI2 was not attributable to increased apoptosis but rather was accompanied by arrest of cell cycle progression in G(1) phase. Finally, we detected citrullinated proteins in normal colon tissue by immunoblot analysis. Our data thus suggest that PADI2 suppresses the proliferation of colonic epithelial cells through catalysis of protein citrullination, and that downregulation of PADI2 expression might therefore contribute to colon carcinogenesis.
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spelling pubmed-54065342017-05-01 Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination Funayama, Ryo Taniguchi, Hajime Mizuma, Masamichi Fujishima, Fumiyoshi Kobayashi, Minoru Ohnuma, Shinobu Unno, Michiaki Nakayama, Keiko Cancer Sci Original Articles Expression of the gene for protein‐arginine deiminase 2 (PADI2) has been shown to be downregulated in colon cancer, with such downregulation being indicative of a poor prognosis in individuals with this disease. We have now examined the expression of PADI2 in matched colon cancer and normal colon tissue specimens as well as in colon cancer cell lines. We found that isoform 1 of PADI2 is the predominant isoform in colon tissue and is downregulated during colon carcinogenesis. Immunohistochemical analysis showed that PADI2 is expressed in normal colonic epithelial cells. Overexpression of PADI2 isoform 1 suppressed the proliferation of colon cancer cells in vitro in association with increased protein citrullination. Expression of a catalytically inactive mutant (C647A) of PADI2 or of PADI2 isoform 2 did not induce such effects, indicating that the protein citrullination activity of PADI2 is required for inhibition of cell growth. The growth defect induced by PADI2 was not attributable to increased apoptosis but rather was accompanied by arrest of cell cycle progression in G(1) phase. Finally, we detected citrullinated proteins in normal colon tissue by immunoblot analysis. Our data thus suggest that PADI2 suppresses the proliferation of colonic epithelial cells through catalysis of protein citrullination, and that downregulation of PADI2 expression might therefore contribute to colon carcinogenesis. John Wiley and Sons Inc. 2017-04-12 2017-04 /pmc/articles/PMC5406534/ /pubmed/28403548 http://dx.doi.org/10.1111/cas.13179 Text en © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Funayama, Ryo
Taniguchi, Hajime
Mizuma, Masamichi
Fujishima, Fumiyoshi
Kobayashi, Minoru
Ohnuma, Shinobu
Unno, Michiaki
Nakayama, Keiko
Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title_full Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title_fullStr Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title_full_unstemmed Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title_short Protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
title_sort protein‐arginine deiminase 2 suppresses proliferation of colon cancer cells through protein citrullination
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406534/
https://www.ncbi.nlm.nih.gov/pubmed/28403548
http://dx.doi.org/10.1111/cas.13179
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