Phosphorylation of tumour suppressor Amotl2 by IKBKE kinase promotes YAP1 signalling, enhancing glioblastoma growth.

Overview

1. Department of Neurosurgery, Henan Provincial People,s Hospital; Zhengzhou University People,s Hospital; Cerebrovascular Disease Hospital, Zhengzhou, Henan, China
2. Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, China
3. Department of Neurosurgery, Yantai Yuhuangding Hospital, Yantai, Shandong, China

Abstract

Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE), a member of the serine/threonine kinase family, is an important oncogene in glioblastoma. IKBKE is involved in the progression of multiple tumours in glioblastoma (GBM), including tumour invasion, migration, and proliferation. Here, we report an IKBKE–angiomotin-like protein 2 (Amotl2)–yes-associated protein 1 (YAP1) axis in which IKBKE inhibits the protein expression of Amotl2, while Amotl2 regulates the nuclear transport of the YAP1 protein, which has been implicated in brain tumour development and progression. Data analysis of multiple IKBKE mRNA databases of glioma and immunohistochemical analysis of a tissue chip indicated that higher IKBKE expression was associated with higher malignancy and shorter survival in glioma patients. IKBKE downregulation significantly inhibited GBM cell proliferation and restrained tumour growth in a GBM mouse model. Moreover, IKBKE phosphorylates Amotl2, promoting Amotl2 ubiquitination and degradation, leading to YAP1 entry into the nucleus and the activation of downstream genes. In summary, our results are the first to show that IKBKE phosphorylates Amotl2 and that GBM cell proliferation is regulated by the IKBKE↑–Amotl2↓–YAP1↑ axis.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE16011, at NCBI GEO; found in the text, “Online databases”

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Funding: added National Natural Science Foundation of China: 81572490; Tianjin Medical University: 300052

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 9 authors, 5 keywords, 43 references.

Cite

This paper

Guo, G., Sun, Y., Hong, R., Lu, Y., Chen, X., Zhao, L., Li, C., Liu, Y., & Huang, Q. (2026). Phosphorylation of tumour suppressor Amotl2 by IKBKE kinase promotes YAP1 signalling, enhancing glioblastoma growth. Frontiers in oncology, 16, 1823895. https://doi.org/10.3389/fonc.2026.1823895

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