Selinexor Disrupts Polyamine Metabolism in Merkel Carcinoma Cells

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with a high propensity for metastasis and mortality. In the United States approximately 80% of MCC cases are associated with Merkel cell polyomavirus (MCPyV). MCPyV drives tumorigenesis through distinct molecular mechanisms compared to UV-induced, virus-negative MCC. This study investigated the eff ects of selinexor, a selective inhibitor of nuclear export, on polyamine metabolism and the oncogenic transcription factor c-Myc in MLK-1 MCPyV-positive MCC cells. MKL-1 cells were treated with selinexor at diff erent concentrations. Immunoblotting and ELISA assays were used to evaluate changes in the expression of polyamine metabolic enzymes and intracellular spermine levels. Selinexor treatment led to a dose-dependent downregulation of key enzymes involved in polyamine biosynthesis and catabolism, and a signifi cant reduction in c-Myc expression and spermine concentration. These fi ndings suggested that selinexor disrupts critical metabolic and oncogenic pathways in MCPyV-positive MCC and supported selinexor’s potential as a novel therapeutic strategy for virus-associated disease.