title: CD47 Promotes Tumor Invasion and Metastasis in Non-small Cell Lung Cancer.
abstract: CD47 is overexpressed in many human cancers, its level positively correlates with tumor invasion and metastasis. However, it is largely unknown whether CD47 overexpression drives metastasis and how CD47 lead to tumor metastasis in non-small cell lung cancer (NSCLC). In this study, we analyzed NSCLC specimens and cell lines, and revealed that CD47 is expressed at a higher level than in tumor-free control samples. Furthermore, increased CD47 expression correlated with clinical staging, lymph node metastasis and distant metastasis. In order to understand the molecular mechanisms underlying CD47 functions, we applied both gain-of-function and loss-of-function approaches in cell lines. The siRNA-mediated downregulation of CD47 inhibited cell invasion and metastasis in vitro, while the overexpression of CD47 by plasmid transfection generated opposite effects. In vivo, CD47-specific shRNA significantly reduced tumor growth and metastasis. On the molecular level, the expression of CD47 correlated with that of Cdc42, both in cell lines and NSCLC specimens. The inhibition of Cdc42 attenuates the invasion and metastasis of CD47-overexpressing cells. These results indicate that Cdc42 is a downstream mediator of CD47-promoted metastasis. Our findings provide first evidence that CD47 is an adverse prognostic factor for disease progression and metastasis, and a promising therapeutic target for NSCLC.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Encheng
authors.initials: E
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Scientific Research Center, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Hematology Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Kang
authors.affiliation: Department of Pathology Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Molecular Medicine Lab, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D051928:CD47 Antigen / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D051928:CD47 Antigen; C497894:CD47 protein, human