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

We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, 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 the matrix metalloproteinase 1 gene (MMP-1), MMP-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.

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

Expression and regulatory effects of murine Schlafen (Slfn) genes in malignant melanoma and renal cell carcinoma.

Mavrommatis E ，Arslan AD ，Sassano A ，Hua Y ，Kroczynska B ，Platanias LC ... -  《-》

Role of interferon {alpha} (IFN{alpha})-inducible Schlafen-5 in regulation of anchorage-independent growth and invasion of malignant melanoma cells.

Katsoulidis E ，Mavrommatis E ，Woodard J ，Shields MA ，Sassano A ，Carayol N ，Sawicki KT ，Munshi HG ，Platanias LC ... -  《-》

Cyclic AMP responsive element-binding protein induces metastatic renal cell carcinoma by mediating the expression of matrix metallopeptidase-2/9 and proteins associated with epithelial-mesenchymal transition.

Wang X ，Cui H ，Lou Z ，Huang S ，Ren Y ，Wang P ，Weng G ... -  《-》

SLFN5 suppresses cancer cell migration and invasion by inhibiting MT1-MMP expression via AKT/GSK-3β/β-catenin pathway.

Human SLFN5 inhibits invasions of IFNα-sensitive renal clear-cell carcinoma and melanoma cells. However, whether this inhibition is confined to these IFNα-sensitive cancers is unclear. Here we show that SLFN5 expressions on both mRNA and protein levels are significantly higher in non/low-invasive cancer cell lines (breast cancer cell line MCF7, colorectal cancer cell line HCT116 and lung cancer cell line A549) than in highly-invasive cancer cell lines (fibrosarcoma cell line HT1080 and renal clear cell cancer cell line 786-0). SLFN5 knockdown in non/low-invasive cancer cell lines enhanced MT1-MMP expression and increased migration and invasion in vitro, and in vivo. Furthermore, SLFN5 overexpression in HT1080 and 786-0 inhibited MT1-MMP expression and repressed migration and invasion. MT1-MMP is instrumental in SLFN5-controlled inhibition of cancer cell migration and invasion, as shown by MT1-MMP-knockdown and -overexpression analyses. SLFN5 knockdown activated AKT/GSK-3β/β-catenin pathway by promotion AKT phosphorylation and subsequent GSK-3β phosphorylation, further β-catenin translocation into nucleus as un-phosphorylated protein at Ser33, 37 and 45 and Thr41 sites. This is the first study to report that SLFN5 inhibits cancer migration and invasiveness in several common cancer cell lines by repressing MT1-MMP expression via the AKT/GSK-3β/β-catenin signalling pathway, suggesting that SLFN5 plays wide inhibitory roles in various cancers.

Wan G ，Liu Y ，Zhu J ，Guo L ，Li C ，Yang Y ，Gu X ，Deng LL ，Lu C ... -  《-》