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Doublecortin-like kinase 2 promotes breast cancer cell invasion and metastasis

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Abstract

Background

Doublecortin-like kinase 2 (DCLK2) is a microtubule-associated protein kinase that participates in neural development and maturation; however, whether it is involved in tumour progression remains unclear.

Methods

DCLK2 overexpression and knockdown clones were established by lentivirus transfection. Western blot, PCR assays and bioinformatics analyses were conducted to observe the expression of DCLK2. CCK8, colony formation, scratch migration and Transwell assays were used to detect cell proliferation, migration and invasion, respectively. Tumour metastasis was evaluated in vivo using a tail vein metastasis model. Bioinformatics analyses were performed to analyse the expression correlation between DCLK2 and TCF4, or EMT markers in breast cancer.

Results

Our data indicate that DCLK2 is highly expressed in breast cancer cells and is associated with poor prognosis. Silencing DCLK2 does not affect the proliferation rate of tumour cells, but significantly suppresses migration and invasion as well as lung metastasis processes. Overexpression of DCLK2 can enhance the migratory and invasive abilities of normal breast epithelial cells. Moreover, TCF4/β-catenin inhibitor LF3 downregulates the expression of DCLK2 and inhibits the migration and invasion of breast cancer cells. Furthermore, we found that the downregulation of DCLK2 blocks the epithelial–mesenchymal transition (EMT) process.

Conclusion

Our study indicates that DCLK2 plays an important role in EMT, cell invasion and metastasis, suggesting that DCLK2 is a potential target for the treatment of metastatic breast cancer.

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Data availability statement

All data supporting the findings of this study are available from the corresponding author on reasonable request.

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Funding

This research was supported by National Natural Science Foundation of China (81672629, 81872168 and 82072925) to JS.

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Author notes

  1. Yanling He, Xiaoqin Dai, Shengnan Li and Xinyuan Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou, China

    Yanling He, Xiaoqin Dai, Shengnan Li, Xinyuan Zhang, Kunxiang Gong, Kai Song & Jian Shi

  2. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Xiaoqin Dai

  3. Guangzhou F.Q. PATHOTECH Co., Ltd, Guangzhou, Guangdong, China

    Shengnan Li

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  1. Yanling He
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Contributions

JS conceived and supervised the study, wrote the manuscript; YH, XD, SL and XZ performed experiments; KG and KS performed bioinformatics analyses; YH, XD and SL analysed data.

Corresponding author

Correspondence to Jian Shi.

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This work has been approved by the Ethics Committee of Southern Medical University and Guangdong Provincial People’s Hospital.

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He, Y., Dai, X., Li, S. et al. Doublecortin-like kinase 2 promotes breast cancer cell invasion and metastasis. Clin Transl Oncol 25, 1102–1113 (2023). https://doi.org/10.1007/s12094-022-03018-z

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  • DOI: https://doi.org/10.1007/s12094-022-03018-z

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