Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2016

12.08.2016 | Original Article – Cancer Research

DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer

verfasst von: Tianbo Gao, Min Wang, Lingling Xu, Tao Wen, Jian Liu, Guangyu An

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
Zurück zum Zitat Kantara C, O’Connell MR, Luthra G, Gajjar A, Sarkar S, Ullrich RL, Singh P (2015) Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Investig 95:100–112. doi:10.1038/labinvest.2014.133 CrossRefPubMed Kantara C, O’Connell MR, Luthra G, Gajjar A, Sarkar S, Ullrich RL, Singh P (2015) Methods for detecting circulating cancer stem cells (CCSCs) as a novel approach for diagnosis of colon cancer relapse/metastasis. Lab Investig 95:100–112. doi:10.​1038/​labinvest.​2014.​133 CrossRefPubMed
Zurück zum Zitat Lin PT, Gleeson JG, Corbo JC, Flanagan L, Walsh CA (2000) DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. J Neurosci 20:9152–9161PubMed Lin PT, Gleeson JG, Corbo JC, Flanagan L, Walsh CA (2000) DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. J Neurosci 20:9152–9161PubMed
Zurück zum Zitat Mirzaei A et al (2015a) Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumour Biol J Int Soc Oncodev Biol Med 36:4801–4810. doi:10.1007/s13277-015-3132-9 CrossRef Mirzaei A et al (2015a) Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumour Biol J Int Soc Oncodev Biol Med 36:4801–4810. doi:10.​1007/​s13277-015-3132-9 CrossRef
Zurück zum Zitat Mirzaei A et al (2015b) A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer? Tumour Biol J Int Soc Oncodev Biol Med. doi:10.1007/s13277-015-3989-7 Mirzaei A et al (2015b) A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer? Tumour Biol J Int Soc Oncodev Biol Med. doi:10.​1007/​s13277-015-3989-7
Zurück zum Zitat Stein U, Schlag PM (2007) Clinical, biological, and molecular aspects of metastasis in colorectal cancer. Recent Results Cancer Res 176:61–80CrossRefPubMed Stein U, Schlag PM (2007) Clinical, biological, and molecular aspects of metastasis in colorectal cancer. Recent Results Cancer Res 176:61–80CrossRefPubMed
Zurück zum Zitat Sureban SM et al (2011) Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanism. J Nanobiotech 9:40. doi:10.1186/1477-3155-9-40 CrossRef Sureban SM et al (2011) Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanism. J Nanobiotech 9:40. doi:10.​1186/​1477-3155-9-40 CrossRef
Metadaten
Titel
DCLK1 is up-regulated and associated with metastasis and prognosis in colorectal cancer
verfasst von
Tianbo Gao
Min Wang
Lingling Xu
Tao Wen
Jian Liu
Guangyu An
Publikationsdatum
12.08.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2016
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2218-0

Weitere Artikel der Ausgabe 10/2016

Journal of Cancer Research and Clinical Oncology 10/2016 Zur Ausgabe

Original Article – Clinical Oncology

Telangiectatic osteosarcoma: a review of 87 cases

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.