Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling.
Trophoblast glycoprotein (TPBG), a 72 kDa glycoprotein was identified using a monoclonal antibody, which specifically binds human trophoblast. The expression of TPBG in normal tissues is limited; however, it is upregulated in numerous types of cancer. When TPBG is expressed at a high level, this usually indicates a poor clinical outcome. In the present study, it was demonstrated that TPBG was more commonly observed in human pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissue. Immunohistochemical analysis of PDAC tissue microarrays indicated that the expression of TPBG in PDAC tissues was closely correlated with the tumor-node-metastasis stage of the tumor. Silencing of TPBG in PDAC cell lines resulted in a decreased ability of cancer cell migration and invasion. Further investigation demonstrated that the Wnt/planar cell polarity signaling pathway was suppressed, as the expression of Wnt5a and the activation of c-Jun N-terminal kinase was inhibited following TPBG knockdown. In conclusion, the present study provided evidence that TPBG is involved in PDAC metastasis, and that TPBG and its associated signaling pathways may be a suitable target for PDAC therapy.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Ping
P
He
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Shuheng
S
Jiang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Mingze
M
Ma
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Yang
Y
Wang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Rongkun
R
Li
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Fang
F
Fang
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Guangang
G
Tian
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China.
Zhigang
Z
Zhang
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D016764:Cell Polarity / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D060449:Wnt Signaling Pathway / Q000235:genetics
D008562:Membrane Glycoproteins; C063709:trophoblastic glycoprotein 5T4, human