A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis.

British Journal of Cancer
Kieun BaeKyong-Ah Yoon

Abstract

Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated. Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed. In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments. Taken together...Continue Reading

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Methods Mentioned

BETA
PCR
transfection
Protein assay
Feature Extraction
xenograft
xenografts

Software Mentioned

ChimeraScan
IncuCyte
FusionMap
GraphPad
GraphPad Prism
NovoExpress
DeFuse
Agilent Feature Extraction

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