Open AccessMetastasis‐associated gene, mag‐1 improves tumour microenvironmental adaptation and potentiates tumour metastasis
Author(s) -
Wang Yan,
Jia Haiquan,
Lin Huiyun,
Tan Xiaogang,
Du Zhiyan,
Chen Huihua,
Xu Yuanji,
Han Xiaoxi,
Zhang Jiakai,
Zhao Siyang,
Yu Xiaodan,
Lu Yinglin
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01633.x
Subject(s) - metastasis , cancer research , biology , cell migration , in vivo , cancer , phenotype , rna interference , in vitro , gene , rna , biochemistry , genetics , microbiology and biotechnology
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 m TOR signalling pathway. We also found that mag‐1 ‐induced metastatic promotion could be abrogated by m TOR 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.