Furin promotes epithelial-mesenchymal transition in pancreatic cancer cells via Hippo-YAP pathway

被引:43
作者
Zhang, Youli [1 ]
Zhou, Meng [1 ]
Wei, Hong [1 ]
Zhou, Hailang [1 ]
He, Junb [1 ]
Lu, Ying [1 ]
Wang, Dawei [1 ]
Chen, Baoding [3 ]
Zeng, Han [2 ]
Peng, Wanxin [2 ]
Du, Fengyi [2 ]
Gong, Aihua [2 ]
Xu, Min [1 ]
机构
[1] Affiliated Hosp Jiangsu Univ, Dept Gastroenterol, Zhenjiang 212013, Jiangsu, Peoples R China
[2] Affiliated Hosp Jiangsu Univ, Sch Med, Dept Cell Biol, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[3] Affiliated Hosp Jiangsu Univ, Dept Ultrasound Diag, Zhenjiang, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Furin; pancreatic cancer cells; epithelial-mesenchymal transition; YAP; D6R; PROPROTEIN CONVERTASE FURIN; TUMOR PROGRESSION; EXPRESSION; GROWTH; ACTIVATION; ENDOPROTEASE; MECHANISMS; PRECURSOR; SURVIVAL; DISEASE;
D O I
10.3892/ijo.2017.3896
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Furin, a well-characterized proprotein convertase, plays an important role in many diseases and links to tumor metastasis. However, the role of Furin in pancreatic cancer progression remains to be elucidated. In the present study, we found that Furin promotes the growth and the epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. First, we found that Furin knockdown significantly inhibited proliferation, invasion and migration in BxPC3 and SW1990 cells, while Furin overexpression promoted the above behavior in PANC1 and PaTu8988 cells. Further evidence revealed that Furin knockdown resulted in the upregulation of E-cadherin (epithelial marker), and the downregulation of N-cadherin and Vimentin (mesenchymal markers) in BxPC3 and SW1990 cells, whereas Furin over expression remarkably led to the opposite effects in PANC1 and PaTu8988 cells. Furthermore, our data showed that Furin knockdown, Furin inhibitor D6R or overexpression significantly affected YAP phosphoration level and total YAP protein level, indicating that Furin was involved in Hippo YAP pathway. It is suggested that Furin promotes epithelial-mesenchymal transition in pancreatic cancer cells probably via Hippo YAP pathway and may be a potential target for anti -pancreatic cancer.
引用
收藏
页码:1352 / 1362
页数:11
相关论文
共 34 条
[21]   Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon [J].
Overholtzer, Michael ;
Zhang, Jianmin ;
Smolen, Gromoslaw A. ;
Muir, Beth ;
Li, Wenmei ;
Sgroi, Dennis C. ;
Deng, Chu-Xia ;
Brugge, Joan S. ;
Haber, Daniel A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (33) :12405-12410
[22]  
Page RE, 2007, CELL ONCOL, V29, P289
[23]   FURIN-DEPENDENT INTRACELLULAR ACTIVATION OF THE HUMAN STROMELYSIN-3 ZYMOGEN [J].
PEI, DQ ;
WEISS, SJ .
NATURE, 1995, 375 (6528) :244-247
[24]   Prognostic Significance of Tumorigenic Cells With Mesenchymal Features in Pancreatic Adenocarcinoma [J].
Rasheed, Zeshaan A. ;
Yang, Jie ;
Wang, Qiuju ;
Kowalski, Jeanne ;
Freed, Irwin ;
Murter, Christopher ;
Hong, Seung-Mo ;
Koorstra, Jan-Bart ;
Rajeshkumar, N. V. ;
He, Xiaobing ;
Goggins, Michael ;
Iacobuzio-Donahue, Christine ;
Berman, David M. ;
Laheru, Daniel ;
Jimeno, Antonio ;
Hidalgo, Manuel ;
Maitra, Anirban ;
Matsui, William .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2010, 102 (05) :340-351
[25]   Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells [J].
Scamuffa, Nathalie ;
Siegfried, Geraldine ;
Bontemps, Yannick ;
Ma, Liming ;
Basak, Ajoy ;
Cherel, Ghislaine ;
Calvo, Fabien ;
Seidah, Nabil G. ;
Khatib, Abdel-Majid .
JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (01) :352-363
[26]   Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects from tumor progression and metastasis [J].
Scamuffa, Nathalie ;
Sfaxi, Fatma ;
Ma, Jia ;
Lalou, Claude ;
Seidah, Nabil ;
Calvo, Fabien ;
Khatib, Abdel-Majid .
CARCINOGENESIS, 2014, 35 (03) :528-536
[27]   The activation and physiological functions of the proprotein convertases [J].
Seidah, Nabil G. ;
Mayer, Gaetan ;
Zaid, Ahmed ;
Rousselet, Estelle ;
Nassoury, Nasha ;
Poirier, Steve ;
Essalmani, Rachid ;
Prat, Annik .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (6-7) :1111-1125
[28]   KRAS and YAP1 Converge to Regulate EMT and Tumor Survival [J].
Shao, Diane D. ;
Xue, Wen ;
Krall, Elsa B. ;
Bhutkar, Arjun ;
Piccioni, Federica ;
Wang, Xiaoxing ;
Schinzel, Anna C. ;
Sood, Sabina ;
Rosenbluh, Joseph ;
Kim, Jong W. ;
Zwang, Yaara ;
Roberts, Thomas M. ;
Root, David E. ;
Jacks, Tyler ;
Hahn, William C. .
CELL, 2014, 158 (01) :171-184
[29]   The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model [J].
Sun, Xiaowei ;
Essalmani, Rachid ;
Seidah, Nabil G. ;
Prat, Annik .
MOLECULAR CANCER, 2009, 8 :73
[30]   Epithelial-Mesenchymal Transitions in Development and Disease [J].
Thiery, Jean Paul ;
Acloque, Herve ;
Huang, Ruby Y. J. ;
Angela Nieto, M. .
CELL, 2009, 139 (05) :871-890