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

• Yanling He ^[1] ; Xiaoqin Dai ^[1] ; Shengnan Li ^[1] ; Xinyuan Zhang ^[1] ; Kunxiang Gong ^[1] ; Kai Song ^[1] ; Jian Shi ^[1]
  1. [1] Southern Medical University

     Southern Medical University

     China

     
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 4 (April), 2023, págs. 1102-1113
• Idioma: inglés
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• Resumen

  • 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.