A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis

Scott Valastyan, Ferenc Reinhardt, Nathan Benaich, Diana Calogrias, A. Szász, Zhigang C. Wang, Jane E. Brock, Andrea L. Richardson, Robert A. Weinberg

Research output: Contribution to journalArticle

701 Citations (Scopus)

Abstract

MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.

Original languageEnglish
Pages (from-to)1032-1046
Number of pages15
JournalCell
Volume137
Issue number6
DOIs
Publication statusPublished - Jun 12 2009

Fingerprint

MicroRNAs
Tumors
Breast Neoplasms
Neoplasm Metastasis
Genes
Cells
Porifera
Neoplasms
Phenotype
Survival

Keywords

  • CELLBIO
  • HUMDISEASE
  • RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Valastyan, S., Reinhardt, F., Benaich, N., Calogrias, D., Szász, A., Wang, Z. C., ... Weinberg, R. A. (2009). A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis. Cell, 137(6), 1032-1046. https://doi.org/10.1016/j.cell.2009.03.047

A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis. / Valastyan, Scott; Reinhardt, Ferenc; Benaich, Nathan; Calogrias, Diana; Szász, A.; Wang, Zhigang C.; Brock, Jane E.; Richardson, Andrea L.; Weinberg, Robert A.

In: Cell, Vol. 137, No. 6, 12.06.2009, p. 1032-1046.

Research output: Contribution to journalArticle

Valastyan, S, Reinhardt, F, Benaich, N, Calogrias, D, Szász, A, Wang, ZC, Brock, JE, Richardson, AL & Weinberg, RA 2009, 'A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis', Cell, vol. 137, no. 6, pp. 1032-1046. https://doi.org/10.1016/j.cell.2009.03.047
Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász A, Wang ZC et al. A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis. Cell. 2009 Jun 12;137(6):1032-1046. https://doi.org/10.1016/j.cell.2009.03.047
Valastyan, Scott ; Reinhardt, Ferenc ; Benaich, Nathan ; Calogrias, Diana ; Szász, A. ; Wang, Zhigang C. ; Brock, Jane E. ; Richardson, Andrea L. ; Weinberg, Robert A. / A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis. In: Cell. 2009 ; Vol. 137, No. 6. pp. 1032-1046.
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