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
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Schlafen family is a prognostic biomarker and corresponds with immune infiltration in gastric cancer.
The Schlafen (SLFN) gene family plays an important role in immune cell differentiation and immune regulation. Previous studies have found that the increased SLFN5 expression in patients with intestinal metaplasia correlates with gastric cancer (GC) progression. However, no investigation has been conducted on the SLFN family in GC. Therefore, we systematically explore the expression and prognostic value of SLFN family members in patients with GC, elucidating their possible biological function and its correlation with tumor immune cells infiltration. TCGA database results indicated that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN13 expression was significantly higher in GC. The UALCAN and KM plotter databases indicated that enhanced the SLFN family expression was associated with lymph node metastasis, tumor stage, and tumor grade and predicted an adverse prognosis. cBioportal database revealed that the SLFN family had a high frequency of genetic alterations in GC (about 12%), including mutations and amplification. The GeneMANIA and STRING databases identified 20 interacting genes and 16 interacting proteins that act as potential targets of the SLFN family. SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 may be implicated in the immunological response, according to Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, Timer and TISIDB databases indicate that SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 are involved in the immune response. Furthermore, Timer, TCGA, and TISIDB databases suggested that the SLFN5, SLFN11, SLFN12, SLFN12L, and SLFN14 expression in GC is highly linked with immune cell infiltration levels, immune checkpoint, and the many immune cell marker sets expression. We isolated three samples of peripheral blood mononuclear cell (PBMC) and activated T cells; the results showed the expression of SLFN family members decreased significantly when T cell active. In conclusion, the SLFN family of proteins may act as a prognostic indicator of GC and is associated with immune cell infiltration and immune checkpoint expression in GC. Additionally, it may be involved in tumor immune evasion by regulating T cell activation.
Xu J
，Chen S
，Liang J
，Hao T
，Wang H
，Liu G
，Jin X
，Li H
，Zhang J
，Zhang C
，He Y
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《Frontiers in Immunology》
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