Human Schlafen 5 (SLFN5) is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma (RCC) Cells

There is some emerging evidence that members of the Schlafen (SLFN) family of proteins mediate antineoplastic responses, but the mechanisms accounting for these effects are not known. We provide evidence that human SLFN5, an interferon (IFN)- inducible member of the family, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of matrix metalloproteinases (MMP)-1 and -13 and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Overall design: Examination of 2 SLFN5 knockdown cells and 2 controls, in triplicate.

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Sassano A, Mavrommatis E, Arslan AD, Kroczynska B, Beauchamp EM, Khuon S, Chew TL, Green KJ, Munshi HG, Verma AK, Platanias LC