XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors

Islam, R.; Wladhaus, A.; Bollen, I.; Descher, L.; Shalan, A.; Balde, V. A. A.; Liesen, A.; Kovacevic, A.; Merges, G. E.; Kristiansen, G.; Schorle, H.

doi:10.64898/2026.09.14.750914

bioRxiv · 10.64898/2026.09.14.750914

XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors

Islam, R.·Wladhaus, A.·Bollen, I.·Descher, L.·Shalan, A.·Balde, V. A. A.·Liesen, A.·Kovacevic, A.·Merges, G. E.·Kristiansen, G.·Schorle, H.

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Abstract

Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. Despite high cure rates with cisplatin-based chemotherapy, resistance and long-term toxicities remain clinical challenges in TGCTs. Selinexor, an FDA-approved XPO1 inhibitor, has demonstrated anti-tumor activity in other cancers, but its potential in TGCTs remains unknown. Objective: We investigated the antitumor effects of selinexor in TGCT cell lines. Materials and methods: XPO1 RNA expression, protein abundance and localization were evaluated by immunohistochemistry in TGCT tissue microarrays and non-neoplastic testicular tissues, and by meta-analysis of publicly available gene-expression microarray datasets from normal testis, primary TGCT specimens as well as TGCT cell lines. Selinexor effects on cell viability, cell-cycle distribution and apoptosis were evaluated using XTT assay and flow cytometry. p53 and p21 expression and localization were analyzed by Western blotting and Immunofluorescence. Results: XPO1 expression was heterogeneous across normal testis, TGCT tissues and cell lines. Yet, selinexor reduced TGCT cell viability and induced G1 or G2/M cell-cycle arrest, apoptosis, increased total p53 and p21 protein levels, and their nuclear accumulation. Of note, control fibroblast exhibited limited sensitivity to selinexor. Discussion and conclusion: Our findings demonstrate that inhibition of XPO1 with selinexor might be potential therapeutic strategy for TGCTs.

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Islam, R., Wladhaus, A., Bollen, I., Descher, L., Shalan, A., Balde, V. A. A., Liesen, A., Kovacevic, A., Merges, G. E., Kristiansen, G., Schorle, H.. 2026-09-20. XPO1 Inhibition by Selinexor Induces Nuclear p53 and p21 Accumulation, Cell-Cycle Arrest and Apoptosis in Testicular Germ Cell Tumors. https://doi.org/10.64898/2026.09.14.750914

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