Metastasis‐associated gene, mag‐1 improves tumour microenvironmental adaptation and potentiates tumour metastasis

Journal of Cellular and Molecular Medicine

Yan Wang¹  Haiquan Jia²  Huiyun Lin²  Xiaogang Tan²  Zhiyan Du¹  Huihua Chen²  Yuanji Xu²  Xiaoxi Han²  Jiakai Zhang¹  Siyang Zhao¹  Xiaodan Yu² 

[1] Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China;Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China

关键词: metastasis‐associated gene;    tumour microenvironment;    HIF‐1α;    mTOR signalling pathway;    tumour metastasis;   

DOI  :  10.1111/j.1582-4934.2012.01633.x

来源: Wiley

【 摘 要 】

Abstract

Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti-metastatic therapies. We previously identified a novel metastasis-associated gene 1 (mag-1) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag-1 and showed that it promoted cell migration, adhesion and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1 integrates dual regulating mechanisms through the stabilization of HIF-1α and the activation of mTOR signalling pathway. We also found that mag-1-induced metastatic promotion could be abrogated by mTOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag-1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment.

【 授权许可】

Unknown   
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd