PMID- 29603227
OWN - NLM
STAT- MEDLINE
DCOM- 20190114
LR  - 20190114
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 143
IP  - 5
DP  - 2018 Sep 1
TI  - PLOD2 as a potential regulator of peritoneal dissemination in gastric cancer.
PG  - 1202-1211
LID - 10.1002/ijc.31410 [doi]
AB  - Peritoneal dissemination is the most common metastatic pattern in advanced 
      gastric cancer (GC) and has a very poor prognosis. However, its molecular 
      mechanism has not been elucidated. Our study investigated genes associated with 
      peritoneal dissemination of GC. We performed combined expression analysis of 
      metastatic GC cell lines and identified Procollagen-lysine, 2-oxoglutarate 
      5-dioxygenase2 (PLOD2) as a potential regulator of peritoneal dissemination. 
      PLOD2 is regulated by hypoxia-inducible factor-1 (HIF-1) and mediates 
      extracellular matrix remodeling, alignment, and mechanical properties. We 
      analyzed PLOD2 expression immunohistochemically in 179 clinical samples, and 
      found high PLOD2 expression to be significantly associated with peritoneal 
      dissemination, leading to poor prognosis. In an in vivo-collected metastatic cell 
      line, downregulation of PLOD2 by siRNA reduced invasiveness and migration. 
      Hypoxia upregulated PLOD2 mediated by HIF-1, and promoted invasiveness and 
      migration. After exposure to hypoxia, a cell line transfected with siPLOD2 
      exhibited significantly suppressed invasiveness and migration, despite high HIF-1 
      expression. These findings indicate that PLOD2 is a regulator of, and candidate 
      therapeutic target for peritoneal dissemination of GC. Although peritoneal 
      dissemination of GC has a very poor prognosis, its molecular mechanism has not 
      been elucidated. We identified PLOD2 regulated by HIF-1 as a potential regulator 
      of peritoneal dissemination of GC. Finally, we showed that PLOD2 promotes cell 
      invasiveness and migration in GC under hypoxia and lead to peritoneal 
      dissemination of GC.
CI  - (c) 2018 UICC.
FAU - Kiyozumi, Yuki
AU  - Kiyozumi Y
AUID- ORCID: 0000-0003-4574-265X
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Iwatsuki, Masaaki
AU  - Iwatsuki M
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Kurashige, Junji
AU  - Kurashige J
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Ogata, Yoko
AU  - Ogata Y
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Yamashita, Kohei
AU  - Yamashita K
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Koga, Yuki
AU  - Koga Y
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Toihata, Tasuku
AU  - Toihata T
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Hiyoshi, Yukiharu
AU  - Hiyoshi Y
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Ishimoto, Takatsugu
AU  - Ishimoto T
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Baba, Yoshifumi
AU  - Baba Y
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Miyamoto, Yuji
AU  - Miyamoto Y
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Yoshida, Naoya
AU  - Yoshida N
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
FAU - Yanagihara, Kazuyoshi
AU  - Yanagihara K
AD  - Division of Translational Research, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 
      277-8577, Japan.
FAU - Mimori, Koshi
AU  - Mimori K
AD  - Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 
      874-0838, Japan.
FAU - Baba, Hideo
AU  - Baba H
AUID- ORCID: 0000-0002-1750-5318
AD  - Department of Gastroenterological Surgery, Kumamoto University, Graduate School 
      of Medical Sciences, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180420
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 1.14.11.4 (PLOD2 protein, human)
RN  - EC 1.14.11.4 (Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase)
SB  - IM
MH  - Aged
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Cell Hypoxia
MH  - *Cell Movement
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Lymphatic Metastasis
MH  - Male
MH  - Neoplasm Invasiveness
MH  - Neoplasm Recurrence, Local/genetics/metabolism/*pathology
MH  - Peritoneal Neoplasms/genetics/metabolism/*secondary
MH  - Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics/*metabolism
MH  - Prognosis
MH  - Stomach Neoplasms/genetics/metabolism/*pathology
MH  - Survival Rate
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - HIF-1
OT  - PLOD2
OT  - gastric cancer
OT  - hypoxia
OT  - peritoneal dissemination
EDAT- 2018/04/01 06:00
MHDA- 2019/01/15 06:00
CRDT- 2018/04/01 06:00
PHST- 2017/10/16 00:00 [received]
PHST- 2018/03/09 00:00 [revised]
PHST- 2018/03/20 00:00 [accepted]
PHST- 2018/04/01 06:00 [pubmed]
PHST- 2019/01/15 06:00 [medline]
PHST- 2018/04/01 06:00 [entrez]
AID - 10.1002/ijc.31410 [doi]
PST - ppublish
SO  - Int J Cancer. 2018 Sep 1;143(5):1202-1211. doi: 10.1002/ijc.31410. Epub 2018 Apr 
      20.