TY - JOUR
T1 - Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H
AU - Shibayama, Yuki
AU - Takahashi, Kazuo
AU - Yamaguchi, Hisateru
AU - Yasuda, Jun
AU - Yamazaki, Daisuke
AU - Rahman, Asadur
AU - Fujimori, Takayuki
AU - Fujisawa, Yoshihide
AU - Takai, Shinji
AU - Furukawa, Toru
AU - Nakagawa, Tsutomu
AU - Ohsaki, Hiroyuki
AU - Kobara, Hideki
AU - Wong, Jing Hao
AU - Masaki, Tsutomu
AU - Yuzawa, Yukio
AU - Kiyomoto, Hideyasu
AU - Yachida, Shinichi
AU - Fujimoto, Akihiro
AU - Nishiyama, Akira
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - (Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.
AB - (Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.
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U2 - 10.1038/s42003-020-01434-x
DO - 10.1038/s42003-020-01434-x
M3 - Article
C2 - 33247206
AN - SCOPUS:85096697218
SN - 2399-3642
VL - 3
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 724
ER -
