KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival

R Hatami, Anieta Sieuwerts, S Izadmehr, Z Yao, RF Qiao, L Papa, Maxime Look, Marcel Smid, J Ohlssen, AC Levine, D Germain, D Burstein, A Kirschenbaum, A DiFeo, John Foekens, G Narla

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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.
Original languageUndefined/Unknown
JournalScience Translational Medicine
Volume5
Issue number169
DOIs
Publication statusPublished - 2013

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