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Sci Transl Med. 2013 Jan 23;5(169):169ra12. doi: 10.1126/scitranslmed.3004688.

KLF6-SV1 drives breast cancer metastasis and is associated with poor survival.

Author information

1
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.

Abstract

Metastasis is the major cause of cancer mortality. A more thorough understanding of the mechanisms driving this complex multistep process will aid in the identification and characterization of therapeutically targetable genetic drivers of disease progression. We demonstrate that KLF6-SV1, an oncogenic splice variant of the KLF6 tumor suppressor gene, is associated with increased metastatic potential and poor survival in a cohort of 671 lymph node-negative breast cancer patients. KLF6-SV1 overexpression in mammary epithelial cell lines resulted in an epithelial-to-mesenchymal-like transition and drove aggressive multiorgan metastatic disease in multiple in vivo models. Additionally, KLF6-SV1 loss-of-function studies demonstrated reversion to an epithelial and less invasive phenotype. Combined, these findings implicate KLF6-SV1 as a key driver of breast cancer metastasis that distinguishes between indolent and lethal early-stage disease and provides a potential therapeutic target for invasive breast cancer.

PMID:
23345610
PMCID:
PMC4661785
DOI:
10.1126/scitranslmed.3004688
[Indexed for MEDLINE]
Free PMC Article

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