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2017 ; 108
(4
): 713-718
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Protein-arginine deiminase 2 suppresses proliferation of colon cancer cells
through protein citrullination
#MMPMID28403548
Funayama R
; Taniguchi H
; Mizuma M
; Fujishima F
; Kobayashi M
; Ohnuma S
; Unno M
; Nakayama K
Cancer Sci
2017[Apr]; 108
(4
): 713-718
PMID28403548
show ga
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.