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Cellular and Molecular Biology

STK32C activated IL-6/JAK2/STAT3 signaling and promoted tumor angiogenesis

British Journal of Cancer volume 134, pages 60–71 (2026)Cite this article

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Abstract

Background

Angiogenesis is essential for colorectal cancer (CRC) progression. The role of serine/threonine kinase STK32C in this process remains unclear.

Methods

STK32C expression was examined in CRC tissues and correlated with patient prognosis. In vitro assays evaluated endothelial proliferation, migration, and tube formation. Mechanisms were studied using immunoprecipitation, western blotting, and gene set enrichment analysis. In vivo, xenograft and Matrigel plug assays assessed tumor growth and angiogenesis.

Results

STK32C was markedly overexpressed in CRC and associated with poor outcomes. Overexpression promoted endothelial angiogenic behaviors, while knockout suppressed them. Mechanistically, STK32C directly phosphorylated STAT3 at Thr196, enhancing its binding to JAK2 and activating IL-6/JAK2/STAT3 signaling. In vivo, STK32C depletion reduced tumor growth, VEGF-A expression, and microvessel density, confirming its pro-angiogenic function. STK32C-mediated tumor angiogenesis relied on STAT3 Thr196 phosphorylation.

Conclusions

STK32C acts as a pro-angiogenic driver in CRC by activating IL-6/JAK2/STAT3 signaling via STAT3 Thr196 phosphorylation. Its strong association with poor prognosis highlights STK32C as a potential biomarker and therapeutic target in anti-angiogenic therapy.

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Fig. 1: The expression of STK32C was upregulated and associated with tumour angiogenesis and the poor prognosis in colorectal cancer.
Fig. 2: Knockdown of STK32C inhibited tumour angiogenesis in vitro.
Fig. 3: STK32C positively promoted the activation of the STAT3 signalling pathway.
Fig. 4: STK32C phosphorylated STAT3 and regulated IL-6/JAK2/STAT3 pathway.
Fig. 5: STK32C-mediated tumour angiogenesis relied on STAT3 T196 phosphorylation.
Fig. 6: Targeting STK32C inhibited tumour growth and angiogenesis in vivo.

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Data availability

The datasets and materials utilised in this research are fully provided within the manuscript.

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Acknowledgements

No additional acknowledgements to report.

Funding

This research was supported by the Natural Science Foundation of Shandong Province (Grant No. R2022MH194).

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Authors and Affiliations

  1. Department of General Surgery, Qilu Hospital of Shandong University, JiNan, China

    Xin Zhang, Mingxin Jin, Yali Chu, Fengjun Liu, Hui Qu & Cheng Chen

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  1. Xin Zhang
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  2. Mingxin Jin
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  5. Hui Qu
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  6. Cheng Chen
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Contributions

ZX and CC conceptualised the study and prepared the manuscript draft. ZX and JMX carried out the experiments and performed data analysis. CYL contributed to data acquisition and analysis. LFJ and QH oversaw the project and provided guidance.

Corresponding author

Correspondence to Cheng Chen.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

This study was reviewed and approved by the Ethical Review Committee of Qilu Hospital, Shandong University (Approval No. KYLL-2021(ZM)-209). Informed consent was obtained from all patients involved in the study. This study was performed in accordance with the Declaration of Helsinki.

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Zhang, X., Jin, M., Chu, Y. et al. STK32C activated IL-6/JAK2/STAT3 signaling and promoted tumor angiogenesis. Br J Cancer 134, 60–71 (2026). https://doi.org/10.1038/s41416-025-03245-5

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