Doublecortin-like kinase 1 isoform 4 (DCLK1-iso4) (DCLK1-iso4)

Doublecortin-like kinase 1 (DCLK1) isoform 4, frequently identified as the short isoform (DCLK1-S), is a serine/threonine protein kinase that serves as a pivotal marker and regulator of cancer stem cells (CSCs) (UniProt O15075). Unlike the long isoform (DCLK1-L) which is essential for neurogenesis, isoform 4 is transcribed from an internal promoter and is specifically overexpressed in various solid tumors, including colorectal and pancreatic cancers (PubMed: 23303383). It plays a significant role in promoting the epithelial-mesenchymal transition (EMT), enhancing tumor cell migration, and maintaining the self-renewal capacity of CSCs (PubMed: 26823719). Because DCLK1-S is often absent in normal intestinal stem cells but highly expressed in tumor-initiating cells, it is considered a highly specific therapeutic target for eliminating the root of cancer recurrence (PubMed: 22246324). Pharmacological inhibition of DCLK1-S using small molecules like DCLK1-IN-1 has shown promise in reducing tumor growth and sensitizing cells to chemotherapy (PubMed: 31110014). Consequently, this isoform is a focus of intense research for developing targeted therapies that spare healthy tissues while effectively treating metastatic disease.

Other names

DCLK1-SShort isoform of DCLK1DCAMKL1 isoform 4Doublecortin-like kinase 1 short form

Inhibition of serine/threonine kinase activity