Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation and potentiates tumour metastasis
Corresponding Author
Yan Wang
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Correspondence to: Ying-Lin Lu or Yan Wang, Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Tel.: +8610-68166874
Fax: +8610-68166874
E-mails: [email protected], [email protected]
Search for more papers by this authorHaiquan Jia
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Search for more papers by this authorHuiyun Lin
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Search for more papers by this authorXiaogang Tan
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorZhiyan Du
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorHuihua Chen
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorYuanji Xu
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorXiaoxi Han
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorJiakai Zhang
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorSiyang Zhao
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorXiaodan Yu
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorCorresponding Author
Yinglin Lu
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Correspondence to: Ying-Lin Lu or Yan Wang, Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Tel.: +8610-68166874
Fax: +8610-68166874
E-mails: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Yan Wang
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Correspondence to: Ying-Lin Lu or Yan Wang, Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Tel.: +8610-68166874
Fax: +8610-68166874
E-mails: [email protected], [email protected]
Search for more papers by this authorHaiquan Jia
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Search for more papers by this authorHuiyun Lin
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
These authors contributed equally to this work.Search for more papers by this authorXiaogang Tan
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorZhiyan Du
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorHuihua Chen
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorYuanji Xu
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorXiaoxi Han
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorJiakai Zhang
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorSiyang Zhao
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorXiaodan Yu
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Search for more papers by this authorCorresponding Author
Yinglin Lu
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China
Department of Pathobiology, Institute of Basic Medical Sciences, Beijing, China
Correspondence to: Ying-Lin Lu or Yan Wang, Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
Tel.: +8610-68166874
Fax: +8610-68166874
E-mails: [email protected], [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| jcmm1633-sup-0001-DataS1.docWord document, 38.5 KB | Data S1 Materials and methods. |
| jcmm1633-sup-0002-FigS1.tifimage/tif, 166.8 KB | Fig S1 Analyzing the interference efficiency of stable clones transfected with mag-1-targeted shRNA in mouse breast cancer EMT6 cells. |
| jcmm1633-sup-0003-FigS2.tifimage/tif, 261.5 KB | Fig S2 Analyzing the transfection efficiency and induction of HIF-1α in hypoxia. H1299 cells and COS-7 cells were plated for 18 hrs before transfected by Mega Tran 1.0 (OriGene) according to the manufacturer's instructions. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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