Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling.
Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer.
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Juan
J
Wang
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Beibei
B
Xin
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Hui
H
Wang
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.
Xiaodan
X
He
Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060, China.
Wei
W
Wei
Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Tianjin 300060, China.
Ti
T
Zhang
School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China. Electronic address: zebal2014@163.com.
Xiaohong
X
Shen
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D005755:Gastrins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012333:RNA, Messenger
ABCG2; Gastrin; Pancreatic cancer; Side population cell