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Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways

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Abstract

Purpose

Breast cancer is one of the leading causes of tumor death worldwide in female, and the five-year overall survival of breast cancer patients remains poor. It is an urgent need to seek novel target for its treatment. Synaptotagmin 13 (SYT13) is a synaptic vesicle transporting protein that regulates the malignant phenotypes of various cancers. However, its role in breast cancer is still unclear. The current study aimed to investigate the effects of SYT13 on the progression of breast cancer.

Methods

Twenty-five pairs of breast cancer tissues and non-tumor tissues were obtained to assess the expression of SYT13. We manually modified the expression of SYT13 in MCF-7 and MDA-MB-231 cells. CCK-8 assay, EdU staining, and cell cycle analysis were carried out to measure the proliferated ability of cells. Annexin V/PI and TUNEL assays were used to detect the apoptotic ability of cells. Wound healing and transwell assays were employed to evaluate the migrated and invasive ability of breast cancer cells.

Results

The results revealed that the mRNA and protein levels of SYT13 were higher in breast cancer tissues and cell lines. Knockdown of SYT13 inhibited the cell proliferation and induced cell cycle arrest in G1 phase of MCF-7 cells by downregulating cyclin D1 and CDK4, as well as upregulating p21. The migration and invasion of MCF-7 cells were repressed by the loss of SYT13 via the gain of E-cadherin and the loss of vimentin. Overexpression of SYT13 in MDA-MB-231 cells led to the opposite effects. Silencing of SYT13 induced the apoptosis ability of MCF-7 cells by the upregulation of bax and the downregulation of bcl-2. Moreover, we found that SYT13 depletion suppressed the FAK/AKT signaling pathway. PF573228 (a FAK inhibitor) and MK2206 (an AKT inhibitor) reversed the SYT13 overexpression-induced promotion of proliferation, migration, and invasion of MDA-MB-231 cells.

Conclusion

The results indicated that SYT13 promoted the malignant phenotypes of breast cancer cells by the activation of FAK/AKT signaling pathway.

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Data availability

The data used to support the findings of this study are available from the authors on reasonable request.

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Yi-Dan Zhang and Rui Zhong contributed equally.

Authors and Affiliations

  1. Graduate School, Dalian Medical University, Dalian, People’s Republic of China

    Yi-Dan Zhang, Rui Zhong, Zhen-Xuan Sun & Teng Wang

  2. College of Educational Science and Technology, Shanxi Datong University, Datong, People’s Republic of China

    Jin-Quan Liu

  3. Department of Thyroid Surgery, Dalian Municipal Central Hospital, 826 Xinan Road, Dalian, People’s Republic of China

    Jin-Tao Liu

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  1. Yi-Dan Zhang
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  2. Rui Zhong
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  5. Teng Wang
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Contributions

Y-DZ and RZ: conceptualization, investigation, methodology, and writing—original draft; J-QL: conceptualization and investigation; Z-XS: conceptualization and formal analysis; TW: conceptualization and validation; J-TL: conceptualization, resources, project administration, supervision, and writing—review and editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jin-Tao Liu.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

The study was approved by the Ethics Committee of Dalian Municipal Central Hospital (YN2022-042-01) following the Declaration of Helsinki.

Consent to participate

Twenty-five pairs of breast cancer tissues and normal tissues were obtained from Dalian Municipal Central Hospital. Informed consent was provided by all participates.

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Zhang, YD., Zhong, R., Liu, JQ. et al. Role of synaptotagmin 13 (SYT13) in promoting breast cancer and signaling pathways. Clin Transl Oncol 25, 1629–1640 (2023). https://doi.org/10.1007/s12094-022-03058-5

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  • DOI: https://doi.org/10.1007/s12094-022-03058-5

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