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A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis.
Bae, Kieun; Kim, Jin Hee; Jung, Hyojik; Kong, Sun-Young; Kim, Yun-Hee; Kim, Sunshin; Lee, Geon Kook; Lee, Jin Soo; Lee, Jake June-Koo; Ju, Young Seok; Choi, Yang-Kyu; Yoon, Kyong-Ah.
Afiliação
  • Bae K; College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.
  • Kim JH; College of Health Science, Cheongju University, Cheongju, 28503, Republic of Korea.
  • Jung H; College of Veterinary Medicine, Konkuk University, Seoul, 05029, Republic of Korea.
  • Kong SY; National Cancer Center Graduate School of Cancer Science and Policy, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Kim YH; Research Institute, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Kim S; Hospital, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Lee GK; National Cancer Center Graduate School of Cancer Science and Policy, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Lee JS; Research Institute, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Lee JJ; Research Institute, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Ju YS; Research Institute, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Choi YK; Hospital, National Cancer Center, Goyang, 10408, Gyeonggi, Republic of Korea.
  • Yoon KA; National Cancer Center Graduate School of Cancer Science and Policy, Goyang, 10408, Gyeonggi, Republic of Korea.
Br J Cancer ; 124(1): 290-298, 2021 01.
Article em En | MEDLINE | ID: mdl-33204025
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fusão Oncogênica / Tetraspanina 30 / RNA Longo não Codificante / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Br J Cancer Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fusão Oncogênica / Tetraspanina 30 / RNA Longo não Codificante / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Limite: Animals / Humans Idioma: En Revista: Br J Cancer Ano de publicação: 2021 Tipo de documento: Article