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EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex.
Li, Guo; Ji, Xiao-Dan; Gao, Hong; Zhao, Jiang-Sha; Xu, Jun-Feng; Sun, Zhi-Jian; Deng, Yue-Zhen; Shi, Shuo; Feng, Yu-Xiong; Zhu, Yin-Qiu; Wang, Tao; Li, Jing-Jing; Xie, Dong.
Afiliação
  • Li G; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai 200031, China.
Nat Commun ; 3: 667, 2012 Feb 07.
Article em En | MEDLINE | ID: mdl-22314363
Eph receptors are implicated in regulating the malignant progression of cancer. Here we find that despite overexpression of EphB3 in human non-small-cell lung cancer, as reported previously, the expression of its cognate ligands, either ephrin-B1 or ephrin-B2, is significantly downregulated, leading to reduced tyrosine phosphorylation of EphB3. Forced activation of EphB3 kinase in EphB3-overexpressing non-small-cell lung cancer cells inhibits cell migratory capability in vitro as well as metastatic seeding in vivo. Furthermore, we identify a novel EphB3-binding protein, the receptor for activated C-kinase 1, which mediates the assembly of a ternary signal complex comprising protein phosphatase 2A, Akt and itself in response to EphB3 activation, leading to reduced Akt phosphorylation and subsequent inhibition of cell migration. Our study reveals a novel tumour-suppressive signalling pathway associated with kinase-activated EphB3 in non-small-cell lung cancer, and provides a potential therapeutic strategy by activating EphB3 signalling, thus inhibiting tumour metastasis.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neuropeptídeos / Regulação Neoplásica da Expressão Gênica / Carcinoma Pulmonar de Células não Pequenas / Receptores de Superfície Celular / Proteínas de Ligação ao GTP / Receptor EphB3 / Proteínas Proto-Oncogênicas c-akt / Neoplasias Pulmonares / Proteínas de Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neuropeptídeos / Regulação Neoplásica da Expressão Gênica / Carcinoma Pulmonar de Células não Pequenas / Receptores de Superfície Celular / Proteínas de Ligação ao GTP / Receptor EphB3 / Proteínas Proto-Oncogênicas c-akt / Neoplasias Pulmonares / Proteínas de Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2012 Tipo de documento: Article