Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 16, Issue 12, Pages 3037-3051Publisher
WILEY
DOI: 10.1111/j.1582-4934.2012.01633.x
Keywords
metastasis-associated gene; tumour microenvironment; HIF-1a; mTOR signalling pathway; tumour metastasis
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Funding
- Chinese National Natural Science Foundation [30800418, 30470389, 30570800, 30970742]
- Chinese State Key Projects for Basic Research [2002CB513105, 2009CB552104, 2012CB518200]
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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-1a 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.
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