DCLK1 promotes malignant progression of breast cancer by regulating Wnt/β-Catenin signaling pathway

Y.-L. Wang, Y. Li, Y.-G. Ma, W.-Y. Wu

Department of Thyroid Mammary, First People’s Hospital, Yangquan, China. Wwyii8522858@163.com

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• Oncology

OBJECTIVE: The study was aimed to investigate the expression of doublecortin-like kinase-1 (DCLK1) in breast cancer (BCa) tissues and cells and further study its association with clinicopathology and prognosis of BCa patients.

PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the expression of DCLK1 in 44 BCa tumor tissues, as well as adjacent normal tissues. Also, the interplay between DCLK1 level and clinical data or the prognosis of BCa patients was analyzed. QRT-PCR was further used to verify the level of DCLK1 in BCa cell lines. In addition, the DCLK1 knockdown model was constructed using lentivirus in BCa cell lines. Next, cell counting kit-8 (CCK-8) and cell clone formation and tranwell assays were used to analyze the effect of DCLK1 on the biological function of BCa cells. Finally, it was explored whether DCLK1 can act through the Wnt/β-Catenin signaling pathway.

RESULTS: In this research, qRT-PCR results revealed that the level of DCLK1 in BCa tumor tissues was remarkably higher than in adjacent tissues. Compared to patients with a low-level of DCLK1, the pathology grading in patients with high-level was higher and the overall survival rate was lower. Similarly, proliferation, as well as the invasion and migration ability of cells in DCLK1 knockdown group was remarkably down-regulated when compared to negative control group. Moreover, the Western Blot results revealed that silencing DCLK1 remarkably decreased the expression of key proteins in Wnt/β-Catenin pathways such as β-Catenin, c-myc, and cyclinD1, thereby promoting the malignant progression of BCa. In addition, the Wnt/β-Catenin pathway inhibitor was found to be able to reverse the impact of DCLK1 overexpression on BCa cell proliferative and metastatic capacity.

CONCLUSIONS: DCLK1 expression was found remarkably increased in BCa tissues and closely associated with the pathological stage, as well as poor prognosis of BCa patients. Furthermore, DCLK1 may promote the malignant progression of BCa by inhibiting the Wnt/β-Catenin pathway.

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