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

Raheleh Hatami, Anieta M. Sieuwerts, Sudeh Izadmehr, Zhong Yao, Rui Fang Qiao, Luena Papa, Maxime P. Look, Marcel Smid, Jessica Ohlssen, Alice C. Levine, Doris Germain, David Burstein, Alexander Kirschenbaum, Analisa DiFeo, John A. Foekens, Goutham Narla

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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 languageEnglish
Article number169ra12
JournalScience Translational Medicine
Issue number169
StatePublished - 23 Jan 2013


Dive into the research topics of 'KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival'. Together they form a unique fingerprint.

Cite this