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ECT2 promotes malignant phenotypes through the activation of the AKT/mTOR pathway and cisplatin resistance in cervical cancer

Cancer Gene Therapy volume 30, pages 62–73 (2023)Cite this article

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Abstract

Epithelial cell transforming sequence 2 (ECT2) is expressed at high levels in various malignancies and contributes to malignant phenotypes in cancers. However, ECT2 is still not fully understood regarding its function and carcinogenic mechanism in cervical cancer. This research indicated that ECT2 expression was elevated in cervical cancer based on bioinformatics analysis and clinical specimens. Experiments in vitro and in vivo confirmed that ECT2 knockdown could suppress the proliferation and metastasis of cervical carcinoma cells. In addition, we found that silencing ECT2 could enhance the sensitivity to cisplatin and promote cell apoptosis. Mechanistically, we observed that ECT2 knockdown could inhibit the AKT/mTOR pathway and activate apoptosis, while ECT2 overexpression induced the opposite effect. The relationship between ECT2 and AKT was further confirmed by immunoprecipitation and rescue experiments. We found that the ECT2 and AKT could interact to form a complex, and knockdown AKT could offset all of the effects induced by ECT2. Our study emphasized the key point of ECT2 in the reversal of cisplatin resistance, and ECT2 could become a potential therapeutic target in cervical cancer.

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Fig. 1: ECT2 is highly expressed in cervical cancer.
Fig. 2: ECT2 promotes the malignant phenotype of cervical cancer cells in vitro and vivo.
Fig. 3: ECT2 regulates apoptosis of cervical cancer cells.
Fig. 4: ECT2 promotes cisplatin resistance in cervical cancer in vitro and in vivo.
Fig. 5: ECT2 promotes the malignant progression in cervical cancer through the AKT/mTOR pathway.
Fig. 6: AKT knockdown reverses the anti-apoptosis, proliferation, and AKT/mTOR pathway activating effects induced by ECT2 overexpression.

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Data availability

The datasets generated during and/or analyzed during the current study are available. The RNA-sequencing data has been uploaded in Sequence Read Archive (SRA) (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA814339).

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Acknowledgements

We would like to acknowledge all participants in this study.

Funding

This research was carried out at Qilu hospital of Shangdong University and supported by the Shandong Province Key Research Project (2017CXGC1210), Natural Science Foundation Youth Project of Shandong Province (ZR2021QH044), Youth Innovation Technology Project of Higher School of Jinan (2021 GXRC027), National Natural Science Foundation of China (81902644), Natural Science Foundation of Shandong Province (ZR2019BC059 and ZR2020QH248), and Science and Technology Development Project of Shandong Province (2019GSF108126).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Xiaoli Liu, Junhua Zhang, Shuang Ju, Lu Liu, Yu Sun, Lingyu Guo, Qianwei Zhen, Sai Han, Wei Lu & Youzhong Zhang

  2. Key Laboratory of Gynecologic Oncology of Shandong Province, Jinan, China

    Xiaoli Liu, Junhua Zhang, Shuang Ju, Lu Liu, Yu Sun, Lingyu Guo, Qianwei Zhen, Sai Han, Wei Lu & Youzhong Zhang

  3. Shandong Engineering Laboratory for Urogynecology, Qilu Hospital of Shandong University, Jinan, China

    Xiaoli Liu, Junhua Zhang, Shuang Ju, Lu Liu, Yu Sun, Lingyu Guo, Qianwei Zhen, Sai Han, Wei Lu & Youzhong Zhang

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Contributions

YZ and XL participated in the conception and design of this study, and carried out the experiments. JZ, LL, YS, and WL were mainly responsible for data curation and statistical analysis. SJ, QZ, LG, and SH contributed to the preparation of drafts and the visualization of the work. All the authors participated in manuscript review and approved the final manuscript.

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Correspondence to Youzhong Zhang.

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Ethics approval of this research was granted by the Ethics Committee of Qilu Hospital of Shandong University. The animal study was reviewed and approved by Institute of Zoology, Shandong University.

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Liu, X., Zhang, J., Ju, S. et al. ECT2 promotes malignant phenotypes through the activation of the AKT/mTOR pathway and cisplatin resistance in cervical cancer. Cancer Gene Ther 30, 62–73 (2023). https://doi.org/10.1038/s41417-022-00525-7

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