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DCLK1 inhibition attenuates tumorigenesis and improves chemosensitivity in esophageal squamous cell carcinoma by inhibiting β-catenin/c-Myc signaling

  • Molecular and cellular mechanisms of disease
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Doublecortin-like kinase 1 (DCLK1) is involved in tumorigenesis, tumor growth and metastasis, and epithelial-to-mesenchymal transition in many digestive tract tumors. It is reportedly highly expressed in Barrett’s esophagus and esophageal adenocarcinoma, but its effects on the occurrence and progression of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin-treated cells. Western blot assay revealed that expression of nuclear β-catenin and c-Myc was significantly increased in ESCC tissues and that si-DCLK1 markedly downregulated nuclear β-catenin and c-Myc in Eca109 cells. Treatment with lithium chloride, an activator of β-catenin signaling, partially abolished the si-DCLK1-induced inhibition of proliferation, migration, invasion, and chemoresistance of ESCC cells. These findings suggest that knockdown of DCLK1 may inhibit the progression of ESCC by regulating proliferation, migration, invasion, and chemosensitivity via suppressing the β-catenin/c-Myc pathway, supporting a promising therapeutic target against ESCC.

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Acknowledgments

The authors are grateful to the American Journal Experts for helpful suggestion and highly qualified English language edit.

Funding

Doctoral Research Initiation Fund of Henan Provincial people’s Hospital Post-doctoral Research Initiation Fund of Henan Province.

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Authors and Affiliations

  1. Department of Gastroenterology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China

    Lianqun Zhang & Xiuling Li

  2. Department of Pathology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, 450003, Henan, China

    Shengli Zhou

  3. Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, 475000, Henan, China

    Ertao Guo

  4. Department of Digestive Oncology, The First Affiliated Hospital of Henan University of TCM, Zhengzhou, 450003, Henan, China

    Xiaoqi Chen

  5. Anyang Tumor Hospital, The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, 455000, Henan, China

    Jun Yang

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  1. Lianqun Zhang
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  2. Shengli Zhou
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Correspondence to Xiuling Li.

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Highlights

• DCLK1 is upregulated in ESCC tissues and cells.

• DCLK1 knockdown reduces the proliferation, migration, and invasion of ESCC cells.

• DCLK1 knockdown sensitizes ESCC cells to cisplatin.

• DCLK1 affects ESCC progression via the β-catenin/c-Myc pathway.

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Zhang, L., Zhou, S., Guo, E. et al. DCLK1 inhibition attenuates tumorigenesis and improves chemosensitivity in esophageal squamous cell carcinoma by inhibiting β-catenin/c-Myc signaling. Pflugers Arch - Eur J Physiol 472, 1041–1049 (2020). https://doi.org/10.1007/s00424-020-02415-z

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