High throughput Screening of Primary Versus Metastatic Isogenic Cell Lines Reveals a Novel Role for SNX18 in Migration of Melanoma Cells - ICMS2015 Abstract Submission Form Tumor Microenvironment Conference

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¹Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Israel
²Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Israel
³Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel
⁴Talpiot Medical Leadership Program, Sheba Medical Center, Israel

Melanoma is a high-grade malignant tumor of pigment producing cells. Melanoma aggressiveness is partially measured through its proliferative, invasive, migratory and immune evasive qualities. These qualities vary even among genotypically identical melanoma, thus discriminate primary from metastatic lesions in terms of differential aggressive phenotype. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate mRNA molecules. Their deregulation plays an essential role in cancer development and progression. In order to reveal new players involved in the regulation of aggressive features we employed 3 high-throughput screens for the analysis of 2 isogenic melanoma cell lines which originated from a primary (WM-115) and metastatic (WM-266-4) lesions of the same melanoma patient. We identified 89 proteins, 146 miRNAs and 1492 mRNAs that were differentially expressed (FC≥2) between these cell lines. miRNAs potential targets were predicted (TargetScan, miRDB) and intersected with the differentially expressed proteins and mRNAs followed by literature screen and prioritization. Sorting Nexin18 (SNX18) protein level was ~6 fold down-regulated in the metastatic cell-line. Remarkably, no change in mRNA levels was observed. Moreover, 49 up-regulated miRNAs were predicted to target SNX18. Over-expression of SNX18 in WM-266-4 cell line had no effect on their proliferation rate but showed 2fold decrease in migration kinetics as measured by Real-Time Cell Analysis assay (p-value=1.87E^-25). Preliminary results show similar trend in A375 cells. These results suggest a possible role for SNX18 in migration of melanoma cells. To the best of our knowledge this is the first report of SNX18 in context of cancer-related features. Finding novel molecular players and deciphering their mechanism of action might pave the way towards improved tools for future therapy and better understanding of the malignant transformation process.