Expression of doublecortin and CaM kinase‑like‑1 protein in serrated neoplasia of the colorectum

Morio, Keiko; Yashima, Kazuo; Tamoto, Akihiro; Hosoda, Kohei; Yamamoto, Sohei; Iwamoto, Toschitake; Ikebuchi, Yuichiro; Kawaguchi, Koichiro; Harada, Kiyoshi; Murawaki, Yoshikazu; Isomoto, Hajime

doi:10.3892/br.2017.1017

Cited by 3 publications

(5 citation statements)

References 25 publications

(39 reference statements)

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“…The group reported that sinonasal polyp derived cultures from both submerged epithelia (nondifferentiated) and cultures with biphasic epithelia (air-liquid interface) produced IL-25 after stimulation with IL-13, possibly suggesting that differentiation does not need to occur completely in order for IL-25 production to occur. Indeed, populations of DCAMKL1-positive cells are increased in human serrated colorectal polyps 73 and nonesmall cell lung cancer 74 and have been studied for its prospective role in the epithelial-to-mesenchymal transition. 75 Together, high concentrations of tuft cells or tuft cell-progenitor cells coupled with persistent epithelial barrier perturbation may be important roles in the origination of type 2 inflammation in the upper airway.…”

Section: Tuft Cells Are Enriched In Human Nasal Polyp Tissuementioning

confidence: 99%

Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma

Sell

Ortiz-Carpena

Herbert

et al. 2021

Annals of Allergy, Asthma & Immunology

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Tuft cells are a type of rare epithelial cell present in the respiratory and intestinal tracts, among other locations in humans, rodents, and reptiles.In addition to other functions, tuft cells use components of the taste transduction system to survey the extracellular environment and play a role in pathogen defense by stimulating neighboring ciliated epithelial cells to secrete antimicrobial products.The dominant epithelial source of interleukin-25 and an important source of cysteinyl leukotrienes in the airway, tuft cells have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis with nasal polyps and asthma.An important role of tuft cells is to act as a bridge between innate and adaptive immune responses in driving type 2 inflammation in the airway.Tuft cells cluster into subpopulations, which could play diverse roles in the pathophysiology of different diseases and possibly utilize immunomodulatory effector molecules outside of type 2 inflammatory cytokines.Further studies are needed, particularly on the use of better genetic tools for tracking tuft cell subpopulations to investigate the extent to which different subpopulations of tuft cells contribute to chronic inflammatory diseases.

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Section: Tuft Cells Are Enriched In Human Nasal Polyp Tissuementioning

confidence: 99%

Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma

Sell

Ortiz-Carpena

Herbert

et al. 2021

Annals of Allergy, Asthma & Immunology

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“…This attribute correlated with increased pluripotency and self-renewal ability of cancer cells (21,22). However DCLK1 expression was infrequently detected in serrated tumors of the colorectum (23).…”

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confidence: 96%

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

et al. 2019

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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 ...

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“…35 Herein, we highlighted a mechanism linking a CSCs maker DCLK1 and 5-fluorouracil resistance, and demonstrated that DCLK1 inhibitor suppressed 5-fluorouracil resistant CRC cells through inhibiting CCAR1/β-catenin pathway-mediated cancer stemness. Accumulating evidences showed that DCLK1 was overexpressed in several types of tumours, especially in CRC [9][10][11][12][13][14][15] and pancreatic cancer. 16,17 Besides, elevated levels of DCLK1 were closely correlated with poor outcomes and tumour recurrence and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidences showed that DCLK1 was overexpressed in several types of tumours, especially in CRC [9][10][11][12][13][14][15] and pancreatic cancer. 16,17 And elevated levels of DCLK1 were closely correlated with poorer outcomes and higher rates of tumour recurrence and metastasis.…”

Section: Dclk1 Is Correlated With 5-fluorouracil Resistance In Crcmentioning

confidence: 99%

“…Doublecortin-like kinase 1 (DCLK1) was a microtubuleassociated protein and a member of the calmodulindependent kinase (CaMK) family. 8 Previous studies showed that DCLK1 was overexpressed in many tumours, including colorectal, [9][10][11][12][13][14][15] pancreatic, 16,17 gastric, 18 renal, 19 hepatocellular carcinoma 20 and other cancers. [21][22][23][24][25][26] The elevated levels of DCLK1 were closely correlated with poorer outcomes and tumour recurrence and metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Targeting DCLK1 overcomes 5‐fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β‐catenin pathway‐mediated cancer stemness

Wang

Zhao

Lin

et al. 2022

Clinical & Translational Med

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Background To date, 5‐fluorouracil‐based chemotherapy is very important for locally advanced or metastatic colorectal cancer (CRC). However, chemotherapy resistance results in tumor recurrence and metastasis, which is a major obstacle for treatment of CRC. Methods In the current research, we establish 5‐fluorouracil resistant cell lines and explore the potential targets associated with 5‐fluorouracil resistance in CRC. Moreover, we perform clinical specimen research, in vitro and in vivo experiments and molecular mechanism research, to reveal the biological effects and the mechanism of DCLK1 promoting 5‐fluorouracil resistance, and to clarify the potential clinical value of DCLK1 as a target of 5‐fluorouracil resistance in CRC. Results We discover that doublecortin‐like kinase 1 (DCLK1), a cancer stem cell maker, is correlated with 5‐fluorouracil resistance, and functionally promotes cancer stemness and 5‐fluorouracil resistance in CRC. Mechanistically, we elucidate that DCLK1 interacts with cell cycle and apoptosis regulator 1 (CCAR1) through the C‐terminal domain, and phosphorylates CCAR1 at the Ser343 site, which is essential for CCAR1 stabilisation. Moreover, we find that DCLK1 positively regulates β‐catenin signalling via CCAR1, which is responsible for maintaining cancer stemness. Subsequently, we prove that blocking β‐catenin inhibits DCLK1‐mediated 5‐fluorouracil resistance in CRC cells. Importantly, we demonstrate that DCLK1 inhibitor could block CCAR1/β‐catenin pathway‐mediated cancer stemness and consequently suppresses 5‐fluorouracil resistant CRC cells in vitro and in vivo. Conclusions Collectively, our findings reveal that DCLK1 promotes 5‐fluorouracil resistance in CRC by CCAR1/β‐catenin pathway‐mediated cancer stemness, and suggest that targeting DCLK1 might be a promising method to eliminate cancer stem cells for overcoming 5‐fluorouracil resistance in CRC.

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Expression of doublecortin and CaM kinase‑like‑1 protein in serrated neoplasia of the colorectum

Cited by 3 publications

References 25 publications

Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma

Tuft cells in the pathogenesis of chronic rhinosinusitis with nasal polyps and asthma

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

Targeting DCLK1 overcomes 5‐fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β‐catenin pathway‐mediated cancer stemness

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