Affiliation:
1. Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2. Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA
3. The Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK 73104, USA
Abstract
While significant strides have been made in understanding cancer biology, the enhancement in patient survival is limited, underscoring the urgency for innovative strategies. Epigenetic modifications characterized by hereditary shifts in gene expression without changes to the DNA sequence play a critical role in producing alternative gene isoforms. When these processes go awry, they influence cancer onset, growth, spread, and cancer stemness. In this review, we delve into the epigenetic and isoform nuances of the protein kinase, doublecortin-like kinase 1 (DCLK1). Recognized as a hallmark of tumor stemness, DCLK1 plays a pivotal role in tumorigenesis, and DCLK1 isoforms, shaped by alternative promoter usage and splicing, can reveal potential therapeutic touchpoints. Our discussion centers on recent findings pertaining to the specific functions of DCLK1 isoforms and the prevailing understanding of its epigenetic regulation via its two distinct promoters. It is noteworthy that all DCLK1 isoforms retain their kinase domain, suggesting that their unique functionalities arise from non-kinase mechanisms. Consequently, our research has pivoted to drugs that specifically influence the epigenetic generation of these DCLK1 isoforms. We posit that a combined therapeutic approach, harnessing both the epigenetic regulators of specific DCLK1 isoforms and DCLK1-targeted drugs, may prove more effective than therapies that solely target DCLK1.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference152 articles.
1. Hallmarks of cancer: The next generation;Hanahan;Cell,2011
2. Colorectal cancer: The epigenetic role of microbiome;Sabit;World J. Clin. Cases,2019
3. Influence of the microbiota on epigenetics in colorectal cancer;Sun;Natl. Sci. Rev.,2019
4. ROS-mediated DNA methylation pattern alterations in carcinogenesis;Wu;Curr. Drug Targets,2015
5. Das, D., Karthik, N., and Taneja, R. (2021). Crosstalk Between Inflammatory Signaling and Methylation in Cancer. Front. Cell Dev. Biol., 9.