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.

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doi.org/10.1126/scitranslmed.3004688, hdl.handle.net/1765/39270
Science Translational Medicine
Erasmus MC: University Medical Center Rotterdam

Hatami, R., Sieuwerts, A., Izadmehr, S., Yao, Z., Qiao, R. F., Papa, L., … Narla, G. (2013). KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival. Science Translational Medicine, 5(169), 1–17. doi:10.1126/scitranslmed.3004688