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TRIM14 promotes chemoresistance in gliomas by activating Wnt/β-catenin signaling via stabilizing Dvl2

Oncogene volume 37, pages 5403–5415 (2018)Cite this article

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A Correction to this article was published on 29 August 2018

This article has been updated

Abstract

Gliomas are a lethal class of brain cancer, with a median survival below 15 months in spite of therapeutic advances. The poor prognosis of this disease is largely attributed to acquired chemotherapy resistance, and new strategies are urgently needed to target resistant glioma cells. Herein, our study demonstrated that tripartite motif-containing 14 (TRIM14) overexpressed in glioma specimens (including tissues and cell lines), and that high level of TRIM14 predicted poor outcome of glioma patients. Furthermore, we found that upregulation of TRIM14 in glioma cells conferred chemoresistance to temozolomide in vitro and in vivo; conversely, silencing TRIM14 sensitized glioma cells to temozolomide. These findings demonstrated that TRIM14 stabilized dishevelled (Dvl2) and subsequently activated the canonical Wnt signaling and promoted chemoresistance. Moreover, inhibition of Dvl2 reversed the oncogenic effect of TRIM14 on chemoresistance. Importantly, consistent with the abovementioned results, we found that TRIM14 expression was significantly associated with hyperactivation of canonical Wnt pathway in clinical glioma specimens. Collectively, the study reveals a new molecular mechanism driving chemotherapy resistance in gliomas, and suggests an opportunity to develop novel therapeutic interventions against gliomas.

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  • 29 August 2018

    Following the publication of this article the authors noted the affiliation details for corresponding author Dr. Wei Zhang was listed incorrectly. The correct affiliation is Neurosurgical Research Institute, The First Affiliated Hospital of Guangdong Pharmaceutics University, Guangzhou, China.

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Acknowledgements

This work was supported by Natural Science Foundation of China (Nos. 91740119, 91529301, 91740118, 81530082 and 81621004); Guangzhou Science and Technology Plan Projects (201803010098, 201510010292); Natural Science Foundation of Guangdong Province (2017A030313799); The Fundamental Research Funds for the Central Universities [No. 17ykjc02].

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Author notes

  1. These authors contributed equally: Zhanyao Tan, Libing Song.

Authors and Affiliations

  1. Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Zhanyao Tan, Jinrong Zhu, Geyan Wu, Lixue Cao, Junwei Song & Jun Li

  2. Guangdong Province Key Laboratory of Brain Function and Disease, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Zhanyao Tan, Jinrong Zhu, Geyan Wu, Lixue Cao, Junwei Song & Jun Li

  3. State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China

    Libing Song

  4. Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

    Libing Song

  5. Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China

    Wenjiao Wu

  6. Neurosurgical Research Institute, The First Affiliated Hospital of Guangdong Pharmaceutics University, Guangzhou, China

    Yanqing Zhou & Wei Zhang

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Tan, Z., Song, L., Wu, W. et al. TRIM14 promotes chemoresistance in gliomas by activating Wnt/β-catenin signaling via stabilizing Dvl2. Oncogene 37, 5403–5415 (2018). https://doi.org/10.1038/s41388-018-0344-7

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