Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer.
Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.
Department of Surgery/Gyeongnam Regional Cancer Center, Gyeongsang National University, Jinju, South Korea.
Sang-Ho
SH
Jeong
Gyung Hyuck
GH
Ko
Young Hyun
YH
Cho
Young-Joon
YJ
Lee
Bok-Im
BI
Cho
Woo-Song
WS
Ha
Sang-Kyung
SK
Choi
Jae Won
JW
Kim
Chang Won
CW
Lee
Yoon Seok
YS
Heo
Seok Hwan
SH
Shin
Jiyun
J
Yoo
Soon-Chan
SC
Hong
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D043564:Inorganic Pyrophosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013270:Stomach / Q000201:enzymology / Q000473:pathology*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043564:Inorganic Pyrophosphatase