Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss

Arun, G., Diermeier, S., Akerman, M., Chang, K. C., Wilkinson, J. E., Hearn, S., Kim, Y., MacLeod, A. R., Krainer, A. R., Norton, L., Brogi, E., Egeblad, M., Spector, D. L. (January 2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev, 30 (1). pp. 34-51. ISSN 1549-5477 (Electronic)0890-9369 (Linking) (Public Dataset)

[thumbnail of Paper]
PDF (Paper)
Spector et al Genes Dev 2016.pdf - Published Version

Download (2MB) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/26701265
DOI: 10.1101/gad.270959.115


Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. Furthermore, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT- and Her2/neu-amplified tumor organoids, increased cell adhesion, and loss of migration. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Together, these data demonstrate for the first time a functional role of Malat1 in regulating critical processes in mammary cancer pathogenesis. Thus, Malat1 represents an exciting therapeutic target, and Malat1 ASOs represent a potential therapy for inhibiting breast cancer progression.

Item Type: Paper
Uncontrolled Keywords: Malat1 antisense therapy breast cancer metastasis noncoding RNA tumor differentiation tumor organoids
Subjects: diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA
diseases & disorders > cancer > metastasis
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Program > Signal Transduction
CSHL labs > Egeblad lab
CSHL labs > Krainer lab
CSHL labs > Spector lab
CSHL Cancer Center Program > Cellular Communication in Cancer Program
CSHL Cancer Center Program > Gene Regulation and Inheritance Program
Highlight: Spector, David L.
Depositing User: Matt Covey
Date: 1 January 2016
Date Deposited: 05 Jan 2016 20:34
Last Modified: 26 Oct 2020 15:46
PMCID: PMC4701977
Related URLs:
Dataset ID:
URI: https://repository.cshl.edu/id/eprint/32206

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving