Pleiotropic effects of DCLK1 in cancer and cancer stem cells

Abstract

Doublecortin-like kinase 1 (DCLK1), a protein molecule, has been identified as a tumor stem cell marker in the cancer cells of gastrointestinal, pancreas, and human colon. DCLK1 expression in cancers, such as breast carcinoma, lung carcinoma, hepatic cell carcinoma, tuft cells, and human cholangiocarcinoma, has shown a way to target the DCLK1 gene and downregulate its expression. Several studies have discussed the inhibition of tumor cell proliferation along with neoplastic cell arrest when the DCLK1 gene, which is expressed in both cancer and normal cells, was targeted successfully. In addition, previous studies have shown that DCLK1 plays a vital role in various cancer metastases. The correlation of DCLK1 with numerous stem cell receptors, signaling pathways, and genes suggests its direct or an indirect role in promoting tumorigenesis. Moreover, the impact of DCLK1 was found to be related to the functioning of an oncogene. The downregulation of DCLK1 expression by using targeted strategies, such as embracing the use of siRNA, miRNA, CRISPR/Cas9 technology, nanomolecules, specific monoclonal antibodies, and silencing the pathways regulated by DCLK1, has shown promising results in both in vitro and in vivo studies on gastrointestinal (GI) cancers. In this review, we will discuss about the present understanding of DCLK1 and its role in the progression of GI cancer and metastasis.

The doublecortin-family kinase ZYG-8DCLK1regulates motor activity to achieve proper force balance inC. elegansacentrosomal spindles

“…This is an important finding, since the mammalian homolog of ZYG-8 (DCLK1/doublecortin-like kinase 1) is upregulated in a wide range of cancers, and knockdown studies have suggested that it is required for tumor progression. Because of this, DCLK1 has recently become a target for the development of kinase inhibitors as therapeutics (Chandrakesan et al, 2017; Chhetri et al, 2022; Ferguson et al, 2020; Ge et al, 2021; Westphalen et al, 2017; Westphalen et al, 2016; Weygant et al, 2014) . However, whether kinase activity is essential for DCLK1’s function in cell division was not previously known.…”

Graph Attention Networks for Drug Combination Discovery: Targeting Pancreatic Cancer Genes with RAIN Protocol

“…This suggests that DCLK1 could serve as a potentially favorable target for addressing pancreatic cancer. [77] [78]…”

“…This suggests that DCLK1 could serve as a potentially favorable target for addressing pancreatic cancer. [77] [78] CTNNB1, also referred to as beta-catenin, is a pivotal protein participating in regulating cell adhesion and transcriptional activity of genes. Mutations in the CTNNB1 gene have been detected in diverse cancer forms., including pancreatic cancer.…”

RBM15 m6A modification‐mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling

“…Emerging evidence has revealed that many genes and proteins are abnormally expressed in cancer cells and contribute to cancer progression by regulating cell growth, proliferation, apoptosis, migration, and metastasis 12,13 . Otubain 2 (OTUB2), a deubiquitinase belonging to ovarian tumor (OTU) superfamily, 14 was first discovered in an OTU gene from Drosophila melanogaster 15 .…”

“…and metastasis. 12,13 Otubain 2 (OTUB2), a deubiquitinase belonging to ovarian tumor (OTU) superfamily, 14 was first discovered in an OTU gene from Drosophila melanogaster. 15 As proven by previous studies, OTUB2 exerts oncogenic effects in human cancers.…”