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Fibroblast Activation Protein (FAP) Overexpression Induces Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma by Down-Regulating Dipeptidyl Peptidase 9 (DPP9)

Authors Wu Q, Zhao M, Huang G, Zheng Z, Chen Y, Zeng W, Lv X

Received 23 December 2019

Accepted for publication 2 March 2020

Published 27 March 2020 Volume 2020:13 Pages 2599—2611

DOI https://doi.org/10.2147/OTT.S243417

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Nicola Silvestris


Qing-qing Wu, 1 Meng Zhao, 1 Guang-zhao Huang, 1 Ze-nan Zheng, 1 Yuechuan Chen, 1 Wei-sen Zeng, 2 Xiao-zhi Lv 1

1Department of Oral & Maxillofacial Surgery, NanFang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, People’s Republic of China

Correspondence: Xiao-zhi Lv
Tel +86 20 6164 2025
Email lxzsurgeon@126.com
 
Wei-sen Zeng
Tel +86 20 6164 7073
Email zengws@smu.edu.cn

Purpose: Fibroblast activation protein (FAP) acts as a tumor promoter via epithelial–mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the FAP targeting proteins and explore the precise mechanism by which FAP promotes EMT in OSCC.
Patients and Methods: Proteins interacting with FAP were found and filtered by immunoprecipitation-mass spectrometry (IP-MS). Both DPP9 protein and mRNA were examined in 90 paired OSCC samples and matched normal tissue. DPP9 knockdown was conducted to determine its function in OSCC in vitro and in vivo.
Results: Dipeptidyl peptidase 9 (DPP9) was identified as interacting with FAP intracellularly by IP-MS. The levels of both DPP9 protein and mRNA were down-regulated in OSCC tissue. Lower DPP9 expression was correlated with unfavorable survival rates of OSCC patients. DPP9 knockdown accelerates the proliferation of OSCC cells in vitro and in vivo. Overexpression of FAP leads to a reduction in DPP9 expression. Likewise, DPP9 overexpression reverses the proliferation, migration, invasion and EMT induced by FAP during OSCC.
Conclusion: Our study finds that FAP promotes EMT of OSCC by down-regulating DPP9 in a non-enzymatic manner. FAP-DPP9 pathway could be a potential therapeutic target of OSCC.

Keywords: FAP, DPP9, EMT, OSCC, oral cancer

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