Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells

被引:33
作者
Song, Jingyuan [1 ]
Chen, Xiao [1 ]
Bai, Jin [1 ]
Liu, Qinghua [1 ]
Li, Hui [1 ]
Xie, Jianwan [1 ]
Jing, Hui [1 ]
Zheng, Junnian [1 ,2 ,3 ]
机构
[1] Xuzhou Med Coll, Jiangsu Key Lab Biol Canc Therapy, Xuzhou 221002, Jiangsu, Peoples R China
[2] Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou 221002, Jiangsu, Peoples R China
[3] Xuzhou Med Coll, Affiliated Hosp, Xuzhou 221002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
DDR1; EMT; Biomarker; Renal cancer cells; TYROSINE KINASE; MATRIX-METALLOPROTEINASE; CARCINOMA CELLS; POOR-PROGNOSIS; OVARIAN-CANCER; MESSENGER-RNA; EXPRESSION; INVASION; ANGIOGENESIS; METASTASIS;
D O I
10.1007/s13277-016-5021-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray. The function of DDR1 was then evaluated in vitro using collagen I and DDR1 small interfering RNA (siRNA) to regulate the expression of DDR1 in OS-RC-2 and ACHN renal cancer cells (RCC). DDR1 expression correlated with increased RCC cell migration, invasion, and angiogenesis. Further study revealed that high expression of DDR1 can result in epithelial to mesenchymal transition (EMT) activation. Western blot assay showed that the N-cadherin protein and vimentin were induced while E-cadherin was reduced after DDR1 over expression. Our results suggest that DDR1 is both a prognostic marker for RCCC and a potential functional target for therapy.
引用
收藏
页码:11509 / 11521
页数:13
相关论文
共 50 条
[1]  
ALVES F, 1995, ONCOGENE, V10, P609
[2]   Identification of two novel, kinase-deficient variants of discoidin domain receptor 1: differential expression in human colon cancer cell lines [J].
Alves, F ;
Saupe, S ;
Ledwon, M ;
Schaub, F ;
Hiddemann, W ;
Vogel, WF .
FASEB JOURNAL, 2001, 15 (07) :1321-1323
[3]   Epithelio-mesenchymatous transition and hepatocellular carcinoma [J].
Battaglia, Serena ;
Benzoubir, Nassima ;
Ghigna, Maria-Rosa ;
Guettier, Catherine ;
Brechot, Christian ;
Bourgeade, Marie-Francoise .
ANNALES DE PATHOLOGIE, 2009, 29 :S65-S66
[4]   Discoidin domain receptors in disease [J].
Borza, Corina M. ;
Pozzi, Arnbra .
MATRIX BIOLOGY, 2014, 34 :185-192
[5]   VEGF Exerts an Angiogenesis-Independent Function in Cancer Cells to Promote Their Malignant Progression [J].
Cao, Ying ;
E, Guangqi ;
Wang, Enfeng ;
Pal, Krishnendu ;
Dutta, Shamit K. ;
Bar-Sagi, Dafna ;
Mukhopadhyay, Debabrata .
CANCER RESEARCH, 2012, 72 (16) :3912-3918
[6]   Structure of the Discoidin Domain Receptor 1 Extracellular Region Bound to an Inhibitory Fab Fragment Reveals Features Important for Signaling [J].
Carafoli, Federico ;
Mayer, Marie Cathrin ;
Shiraishi, Kazushige ;
Pecheva, Mira Anguelova ;
Chan, Lai Yi ;
Nan, Ruodan ;
Leitinger, Birgit ;
Hohenester, Erhard .
STRUCTURE, 2012, 20 (04) :688-697
[7]   Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[8]   Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells [J].
Castro-Sanchez, Luis ;
Soto-Guzman, Adriana ;
Guaderrama-Diaz, Margarita ;
Cortes-Reynosa, Pedro ;
Perez Salazar, Eduardo .
CLINICAL & EXPERIMENTAL METASTASIS, 2011, 28 (05) :463-477
[9]   Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials [J].
Coppin, Chris ;
Kollmannsberger, Christian ;
Le, Lyly ;
Porzsolt, Franz ;
Wilt, Timothy J. .
BJU INTERNATIONAL, 2011, 108 (10) :1556-1563
[10]   Cancer - Proteases - invasion and more [J].
Edwards, DR ;
Murphy, G .
NATURE, 1998, 394 (6693) :527-528