LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer

Aldema Sas-Chen, Miriam R. Aure, Limor Leibovich, Silvia Carvalho, Yehoshua Enuka, Cindy Körner, Maria Polycarpou-Schwarz, Sara Lavi, Nava Nevo, Yuri Kuznetsov, Justin Yuan, Francisco Azuaje, Igor Ulitsky, Sven Diederichs, Stefan Wiemann, Zohar Yakhini, Vessela N. Kristensen, Anne Lise Børresen-Dale, Yosef Yarden*, Torill SauerJürgen Geisler, Solveig Hofvind, Tone F. Bathen, Elin Borgen, Olav Engebråten, Øystein Fodstad, Øystein Garred, Gry Aarum Geitvik, Rolf Kåresen, Bjørn Naume, Gunhild Mari Mælandsmo, Hege G. Russnes, Ellen Schlichting, Therese Sørlie, Ole Christian Lingjærde, Kristine Kleivi Sahlberg, Helle Kristine Skjerven, Britt Fritzman, Oslo Breast Cancer Research Consortium (OSBREAC)

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

61 Citations (Scopus)

Abstract

Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal-like subtype associates with increased EGFR signaling, while another, the HER2-enriched subtype, engages a kin of EGFR. Based on the premise that EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we identified multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.

Original languageEnglish
Pages (from-to)1052-1064
Number of pages13
JournalEMBO Molecular Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • biomarkers
  • breast cancer
  • long noncoding RNA
  • migration
  • receptor tyrosine kinase

Fingerprint

Dive into the research topics of 'LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer'. Together they form a unique fingerprint.

Cite this