CDH4 suppresses the progression of salivary adenoid cystic carcinoma via E-cadherin co-expression

// Jian Xie 1, * , Yan Feng 1, * , Ting Lin 1, * , Xiao-Yu Huang 1 , Rui-Huan Gan 1 , Yong Zhao 2 , Bo-Hua Su 1 , Lin-Can Ding 1 , Lin She 1 , Jiang Chen 3 , Li-Song Lin 4 , Xu Lin 5 , Da-Li Zheng 5 , You-Guang Lu 1 1 Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China 2 Department of Pathology, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China 3 Center of Dental Implant, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China 4 Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, Fuzhou, China 5 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China * These authors have contributed equally to this work Correspondence to: Da-Li Zheng, email: dalizheng@mail.fjmu.edu.cn You-Guang Lu, email: fjlyg63@163.com Keywords: CDH4, salivary adenoid cystic carcinoma, CDH1, proliferation, invasion Received: May 23, 2016      Accepted: October 14, 2016      Published: October 22, 2016 ABSTRACT The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0.001). Knockdown of CDH4 expression in vitro promoted the growth, mobility and invasion of SACC cells, and in vivo experiments showed that decreased CDH4 expression enhanced SACC tumorigenicity. Furthermore, CDH4 suppression resulted in down-regulation of E-cadherin (E-cad), which is encoded by CDH1 gene and is a well-known tumor suppressor gene by inhibition of cell proliferation and migration. These results indicate that CDH4 may play a negative role in the growth and metastasis of SACC via co-expression with E-cadherin.