Pyrvinium pamoate targets to multiple vulnerabilities of Merkel cell carcinoma
Among several WNT signaling perturbagens, we identified pyrvinium pamoate, an FDA-approved anthelminthic drug that exhibits anti-tumor abilities in multiple cancers. Through the integration of transcriptomic, network, and molecular analyses, we discovered that pyrvinium is broadly effective against Merkel cell carcinoma cell lines, and it targets multiple proposed MCC tumorigenesis pathways. Our study revealed that pyrvinium exerts anti-tumor activity in MCC not only through perturbing the canonical and non-canonical WNT signaling pathway but also non-specifically inhibiting cell growth - via the activation of the p53-mediated apoptosis pathway, modulation of mitochondrial function, and induction of endoplasmic reticulum (ER) stress. Overall design: Comparative gene expression profiling analysis of RNA-seq data for WaGa/MKL1 cell lines treated with DMSO and 1 µM pyrvinium pamoate for 6h and 24h