title: Metastasis-associated gene, mag-1 improves tumour microenvironmental adaptation and potentiates tumour metastasis.
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.
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences, Beijing, China. yan_way@yahoo.com.cn
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Haiquan
authors.initials: H
authors.lastname: Jia
authors.forename: Huiyun
authors.initials: H
authors.lastname: Lin
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Tan
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Du
authors.forename: Huihua
authors.initials: H
authors.lastname: Chen
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Han
authors.forename: Jiakai
authors.initials: J
authors.lastname: Zhang
authors.forename: Siyang
authors.initials: S
authors.lastname: Zhao
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Yu
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002522:Chlorocebus aethiops; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D059467:Transcriptome; D059016:Tumor Microenvironment
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C521685:GPAT3 protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus