Abstract
Purpose
Metastasis is a primary cause of colorectal cancer (CRC)-related death, and cancer stem cells (CSCs) are thought to be majorly responsible for initiating metastatic behaviors. Doublecortin-like kinase 1 (DCLK1) was recently discovered to be a marker for gastrointestinal CSCs. Here, we aimed to explore whether DCLK1 is associated with CRC metastasis through clinical and in vitro investigations.
Methods
The expression levels of DCLK1 mRNA and protein in human CRC tissues were analyzed through quantitative RT-PCR and immunohistochemistry staining, respectively. Human CRC cell line SW480 was selected to explore the effect of DCLK1 overexpression on cell migration and invasion. Besides, the associations between DCLK1 and epithelial–mesenchymal transition (EMT) were determined.
Results
Compared to normal colorectal tissues, DCLK1 expression was significantly up-regulated in human CRC tissues and correlated well with high lymphatic metastasis and poor prognosis in patients. DCLK1 expression was inversely associated with overall survival in CRC patients. Overexpression of DCLK1 in SW480 cells markedly promoted cell migration and invasion. Furthermore, we validated that DCLK1 could facilitate EMT in cancer cells by up-regulation of the mesenchymal markers Vimentin and ZEB1 and down-regulation of the epithelial marker E-cadherin in SW480 cells.
Conclusions
DCLK1 up-regulation may play a contributory role in CRC metastasis and poor prognosis via activation of EMT. DCLK1 may serve as an independent predictor for CRC prognosis.
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Abbreviations
- DCLK1:
-
Doublecortin-like kinase 1
- CRC:
-
Colorectal cancer
- TCGA:
-
The Cancer Genome Atlas
- AJCC:
-
American Joint Committee on Cancer
- MAPs:
-
Microtuble-associated proteins
- DCX:
-
Doublecortin
- CSCs:
-
Cancer stem cells
- EMT:
-
Epithelial–mesenchymal transition
- TNM:
-
Tumor node metastasis
- ATCC:
-
American Type Culture Collection
- OS:
-
Overall survival
- HR:
-
Hazard ratio
- CI:
-
Confidence interval
- SD:
-
Standard deviation
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Acknowledgments
This work was supported by grants from National Natural Science Foundation of China (No. 81572825, to Guangyu An). Beijing Municipal Health System High-level Talent Training Project (to Tao Wen), Beijing, P. R. China. National Natural Science Foundation of China (Youth fund project, No. 81502384, to Jian Liu).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Tianbo Gao and Min Wang contributed equally to this work.
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Gao, T., Wang, M., Xu, L. et al. DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer. J Cancer Res Clin Oncol 142, 2131–2140 (2016). https://doi.org/10.1007/s00432-016-2218-0
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DOI: https://doi.org/10.1007/s00432-016-2218-0