Increased semaphorin 3c expression promotes tumor growth and metastasis in pancreatic ductal adenocarcinoma by activating the ERK1/2 signaling pathway.
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients. Knockdown of sema3c attenuated proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a pancreatic cancer cell line and reduced PDAC cell tumorigenesis upon xenotransplantation into NOD/SCID mice. Overexpression of sema3c produced the opposite effects and promoted the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Overall, our findings demonstrate that aberrant expression of sema3c is correlated with poor prognosis of PDAC patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway.
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Xuejun
X
Xu
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Zhiping
Z
Zhao
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Shixiang
S
Guo
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Jian
J
Li
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Songsong
S
Liu
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Yu
Y
You
Institute of Immunology, PLA, Third Military Medical University, Chongqing 40038, PR China; Department of Pathophysiology and High Altitude Pathology, Third Military Medical University, Chongqing 400038, PR China. Electronic address: nibingxi@yahoo.com.
Bing
B
Ni
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: whuaizhi@gmail.com.
Huaizhi
H
Wang
Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: bieping@medmail.com.cn.
Ping
P
Bie
D000818:Animals; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
C543908:Sema3C protein, human; D039961:Semaphorins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
EMT; ERK1/2; Pancreatic ductal adenocarcinoma; Sema3c