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bioRxiv · 10.64898/2026.02.20.707140

KRT17 stabilizes EPN1 via inhibiting SMURF1-mediated ubiquitination to modulate Wnt/β-catenin signaling output and stem-like traits in ovarian cancer

Du, G.·Li, B.·Zhao, R.·Tong, H.·He, Y.·Ding, J.
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Abstract

BackgroundOvarian cancer (OC) progression and chemoresistance are closely linked to dysregulated oncogenic signaling, including Wnt/{beta}-catenin pathways that contribute to cancer stem-like traits. However, the upstream mechanisms connecting cytoskeletal regulation to Wn/{beta}-catenin signaling in OC remain incompletely understood. Keratin 17 (KRT17), a type I intermediate filament protein, has been implicated in tumor progression, but its mechanistic role in OC requires clarification. MethodsGene Expression Omnibus (GEO) datasets and clinical specimens were analyzed to assess KRT17 and EPN1 expression and prognostic significance. Functional assays, xenograft models, co-immunoprecipitation, ubiquitination analyses, and rescue experiments with wild-type and ubiquitination-resistant EPN1 mutants were performed to investigate molecular mechanisms. ResultsKRT17 expression was elevated in OC tissues and correlated with poor patient survival. KRT17 depletion suppressed proliferation, migration, stem-like properties, tumor growth, and cisplatin resistance. Mechanistically, KRT17 interacted with EPN1 and weakened its association with the E3 ligase SMURF1, reducing SMURF1-mediated ubiquitination at lysine 107 and preventing proteasomal degradation. Stabilized EPN1 was associated with increased {beta}-catenin abundance and stemness-associated markers, and enhanced self-renewal capacity. ConclusionsThese findings identify a KRT17-EPN1 axis that links intermediate filament dynamics to ubiquitin-dependent regulation of EPN1 stability and Wnt/{beta}-catenin signaling outputs in ovarian cancer.

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Du, G., Li, B., Zhao, R., Tong, H., He, Y., Ding, J.. 2026-02-25. KRT17 stabilizes EPN1 via inhibiting SMURF1-mediated ubiquitination to modulate Wnt/β-catenin signaling output and stem-like traits in ovarian cancer. https://doi.org/10.64898/2026.02.20.707140

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