Hippo signaling pathway in human testis and seminoma: anticancer effect of verteporfin on human seminoma TCam-2 cells

Abstract

Aim: Seminoma and embryonal carcinoma are among the most common germ cell tumors. Verteporfin, a YAP-TEAD inhibitor, has emerged as a potential anticancer agent. This study investigated the localization of Hippo signaling proteins in human testis, seminoma, and non-seminoma tissues, and examined verteporfin’s effects on TCam-2 seminoma cells. Methods: Protein localization in tissues was assessed using immunohistochemistry. TCam-2 cells were treated with various concentrations of verteporfin (1–40 µM) for 24, 48, and 72 h. Protein and gene expression were analyzed via immunofluorescence, western blotting, and qRT-PCR. Results: Hippo pathway proteins showed distinct localization patterns across tissue types. Verteporfin treatment caused a dose- and time-dependent decrease in protein levels without altering mRNA expression. It also induced nuclear-to-cytoplasmic translocation of pathway proteins and reduced cell proliferation, migration, and viability, while simultaneously promoting apoptosis in TCam-2 human seminoma cells. Conclusion: Verteporfin may serve as a promising therapeutic strategy for seminoma by targeting Hippo signaling. These findings support its potential role in personalized treatment approaches for testicular cancer. © 2025 Elsevier B.V., All rights reserved.