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Cellular and Molecular Biology

KSRP-mediated Wnt/β-catenin activation promotes follicular thyroid cancer progression and stemness

British Journal of Cancer volume 133, pages 1111–1121 (2025)Cite this article

Subjects

Abstract

Background

K-homology-type splicing regulatory protein (KSRP) is an RNA-binding protein involved in mRNA decay and translational repression through recognition of adenine–uracil-rich elements. Although KSRP regulates approximately 16% of transcript expression, its role in cancer remains poorly defined.

Methods

KSRP expression was analysed using qPCR, Western blot, and immunohistochemistry. Its functional role in follicular thyroid cancer (FTC) was examined through in vitro and in vivo assays. Luciferase reporter and rescue experiments were performed to elucidate the underlying molecular mechanisms.

Results

KSRP was significantly upregulated in FTC tissues and metastatic cell lines. Functional studies demonstrated that KSRP enhances the invasiveness and stemness of FTC cells. Mechanistically, KSRP promotes nuclear accumulation and transcriptional activity of β-catenin by downregulating the Wnt inhibitors DACT2 and SFRP2.

Conclusion

This study identifies KSRP as an oncogenic factor in FTC that activates Wnt/β-catenin signalling, suggesting its potential as a therapeutic target for FTC patients.

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Fig. 1: Expression of KSRP during the development of FTC.
Fig. 2: High expression of KSRP in FTC-236 cells enhances clonogenic and tumorigenic properties.
Fig. 3: KSRP enhances the metastatic and clonogenic properties of FTC cells.
Fig. 4: KSRP promotes the self-renewal of FTC cells by activating β-catenin.
Fig. 5: KSRP negatively regulates the inhibitors of Wnt signalling to activate β-catenin signalling and promote FTC stemness.

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Data availability

All data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the National RNAi Core Facility at Academia Sinica, Taiwan, for providing shRNA reagents and relevant services.

Funding

This study was supported by the National Science and Technology Council, Taiwan (grant number: 111-2628-B-002-023-MY3), Wan Fang Hospital (grant number: 112-wf-eva-04, 113-wf-swf-06), and Far Eastern Memorial Hospital (grant number: 114-FTN0014).

Author information

Author notes

  1. These authors contributed equally: Ke-Fan Pan, Han-Lin Chou.

Authors and Affiliations

  1. Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ke-Fan Pan, Han-Lin Chou, Wei-Li Wang, Bo-Rong Chen & Kuo-Tai Hua

  2. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Ke-Fan Pan

  3. Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Ke-Fan Pan

  4. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

    Bo-Rong Chen & Ming-Hsun Wu

  5. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    Michael Hsiao

  6. Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan

    Michael Hsiao

  7. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

    Kuo-Tai Hua

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Contributions

Ke-Fan Pan: Study design and Writing - Original draft preparation. Han-Lin Chou: Methodology and Investigation. Wei-Li Wang: Investigation. Bo-Rong Chen: Investigation. Michael Hsiao: Resources. Kuo-Tai Hua: Writing – Review & editing, Supervision, and Project administration. Ming-Hsun Wu: Supervision and Project administration. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Kuo-Tai Hua or Ming-Hsun Wu.

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The authors declare no competing interests.

Ethical approval and consent to participate

This study was approved by the Institutional Review Board of National Taiwan University Hospital (institutional approval number: 201402068RINA), and written informed consent was obtained from all study participants enrolled, and all participants consented to participate in this work. Ethics approval for the animal studies was obtained from the Institutional Animal Care and Use Committee of National Taiwan University’s College of Medicine and College of Public Health (approval number: 20150359), and all procedures were performed in accordance with established guidelines.

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Pan, KF., Chou, HL., Wang, WL. et al. KSRP-mediated Wnt/β-catenin activation promotes follicular thyroid cancer progression and stemness. Br J Cancer 133, 1111–1121 (2025). https://doi.org/10.1038/s41416-025-03142-x

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