Long noncoding RNA MALAT1 suppresses breast cancer metastasis
Top Cited Papers
- 1 December 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 50 (12), 1705-+
- https://doi.org/10.1038/s41588-018-0252-3
Abstract
MALAT1 has previously been described as a metastasis-promoting long noncoding RNA (lncRNA). We show here, however, that targeted inactivation of the Malat1 gene in a transgenic mouse model of breast cancer, without altering the expression of its adjacent genes, promotes lung metastasis, and that this phenotype can be reversed by genetic add-back of Malat1. Similarly, knockout of MALAT1 in human breast cancer cells induces their metastatic ability, which is reversed by re-expression of Malat1. Conversely, overexpression of Malat1 suppresses breast cancer metastasis in transgenic, xenograft, and syngeneic models. Mechanistically, the MALAT1 lncRNA binds and inactivates the prometastatic transcription factor TEAD, preventing TEAD from associating with its co-activator YAP and target gene promoters. Moreover, MALAT1 levels inversely correlate with breast cancer progression and metastatic ability. These findings demonstrate that MALAT1 is a metastasis-suppressing lncRNA rather than a metastasis promoter in breast cancer, calling for rectification of the model for this highly abundant and conserved lncRNA.This publication has 61 references indexed in Scilit:
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the AdultCell Reports, 2012
- The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivityNature, 2012
- The Hippo Signaling Pathway in Development and CancerDevelopmental Cell, 2010
- The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor PhosphorylationMolecular Cell, 2010
- An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patientsBreast Cancer Research and Treatment, 2009
- Role of human noncoding RNAs in the control of tumorigenesisProceedings of the National Academy of Sciences of the United States of America, 2009
- 3′ End Processing of a Long Nuclear-Retained Noncoding RNA Yields a tRNA-like Cytoplasmic RNACell, 2008
- Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient miceTransgenic Research, 2007
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006