The Essential Role of DCLK1 in Pathogenesis, Diagnostic Procedures and Prognostic Stratification of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the second most prevalent type of cancer among males and the third among females. CRC recurrence and poor prognosis may be related to the prevalence of chemotherapy-resistant cancer stem cells (CSCs). Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) protein as a marker of CSC in CRC. This review focuses on the role of DCLK1 in CRC. Long-lived DCLK1-positive tuft cells can function as cancer-initiating cells. Numerous studies have shown DCLK1 overexpression to be significantly correlated with the stage of disease, the presence of metastasis and poor survival rate. DCLK1 may also be used to identify patients at high risk and those with chemotherapy-resistant tumors. DCLK1-specific drugs are examined as potential cancer treatments.Colorectal cancer (CRC) is the second most prevalent cancer type among males and the third among females. The 5-year relative survival rate for patients with CRC is 65% (1). The poor prognosis is related to metastasis, especially distant metastasis to the liver (2). Tumor recurrence and poor prognosis may be relevant to the prevalence of chemotherapy-resistant cancer stem cells (CSC) (3). Recent studies have shown that these cells are associated with maintaining the tumor cell population, metastatic processes and chemotherapy resistance (4). CSCs have the ability for self-renewal and may initiate tumorigenesis. Circulating CSCs have been detected in the bloodstream of patients with cancer (5, 6). There is more and more evidence emphasizing the role of specific markers for CSC detection. They may also serve as targets for cancer therapy in the future. Several CSC markers, such as leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), CD44 and progastrin peptides have been identified so far (7). The role of selected CSC markers is presented in Table I.Recent studies have indicated the role of doublecortin-like kinase 1 (DCLK1) as a potential CSC marker in several tumor types. DCLK1 expression was shown to be correlated with low survival rate in esophageal, breast, and renal cell carcinoma (8-10). DCLK1 + cells were also found in the gastrointestinal tract and were mostly expressed in the lower parts of intestinal crypt epithelium and crypt based columnar cells in normal intestine (11). The role of DCLK1 in CRC has also been highlighted. DCLK1 expression was upregulated in CRC and was associated with CRC metastasis and poor prognosis (12). The discovery of DCLK1 may be used in the future to identify patients at high risk, monitor recurrence and evaluate response to therapy. This protein may also serve as a therapeutic target to improve outcomes. Herein, the Authors focus on the role of DCLK1 in CRC. DCLK1 as an Important Factor in Colorectal CarcinogenesisDCLK1 was first described in the developing brain (3). It was important in neurogenesis, cortical development and migration of neurons especially during fetal development (4, 7). This protein is a serine/threonine-protein kinase which is associated with microtubules and its ...

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer

“…However, some studies have shown that CD44 overexpression has been correlated with worse OS of patients with CRC (Wang et al 2019 , 2017 ). Similarly, several studies show a positive correlation between high DCLK1 expression and CRC clinicopathological characteristics and poor OS (GZIL et al 2019a , b ). However, Dai T. et al’s study reveals that a high DCLK1 expression in CRC tissue could play a protective role against tumor progression and correlates with longer survival time (Dai et al 2018 ).…”

“…Furthermore, it is well known that CSCs are insensitive to the current drug regimens. CSCs in CRC are identified via a group of surface markers, such as CD44, CD133, ANXA2, CD24, DCLK1, Lgr5, ALDH1, Nanog, Oct-4, SOX-2, and EpCAM (Leng et al 2018 ) (Gzil et al 2019a , b ). Some of these markers could have a potential clinical role in predicting pathological stage, therapy resistance, and cancer recurrence in patients with colorectal carcinoma.…”

Sox9, Hopx, and survivin and tuft cell marker DCLK1 expression in normal canine intestine and in intestinal adenoma and adenocarcinoma

“…Very recent studies demonstrated that DCLK1 plays an important role in epithelialmesenchymal transition and is associated with drug resistance as well as poor prognostication of colorectal cancer. 24,32,49,52,68,84 In this investigation, DCLK1 was diffusely expressed in canine intestinal adenomas and infrequently detectable in intestinal adenocarcinomas. In general, papillary CRCs showed a higher expression of DCLK1 in the luminal aspects of the tumor than in the invasive areas.…”

CXCL12/CXCR7/β-arrestin1 Biased Signal Promotes Epithelial-to-Mesenchymal Transition of Colorectal Cancer by Repressing Mirnas Through YAP1 Nuclear Translocation

“…Interestingly, it has been reported that ZEB1 is also a target gene of miR-124-3p and the upregulation of ZEB1 could promote EMT and stemness by acting as the most important EMT-activating transcription factor [39] . DCLK1, a member of the protein kinase superfamily and the double cortin family, is highly expressed in several types of cancers and has been recently identi ed as a tumor stem cell marker in CRC [40,41] .…”