Doublecortin-like kinase 1–gelsolin protein–protein interface (DCLK1–GSN PPI)

The Doublecortin-like kinase 1–gelsolin (DCLK1–GSN) protein–protein interface is an emerging therapeutic target primarily studied in the context of aggressive cancers such as pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer [1, 2]. DCLK1 is a microtubule-associated serine/threonine kinase that serves as a marker for cancer stem cells and a driver of epithelial-mesenchymal transition (EMT) [2, 3]. Recent evidence indicates that DCLK1 isoform 4, which possesses a unique extracellular domain (ECD), interacts directly with plasma gelsolin (pGSN), an actin-binding protein that promotes tumorigenesis and inflammation [1, 4]. This interaction is critical for the non-kinase oncogenic functions of DCLK1, facilitating tumor cell proliferation, migration, and survival [1]. Therapeutic intervention targeting this interface, such as the use of specialized D-peptides (e.g., D-peptide 1) or monoclonal antibodies like CBT-15, aims to disrupt the DCLK1–GSN complex to inhibit metastasis and tumor growth [1, 5]. Targeting this specific protein-protein interface offers a precision oncology approach that may bypass the challenges associated with traditional kinase inhibitors while potentially minimizing systemic toxicity [1, 3].

Other names

DCLK1-Gelsolin complexDCLK1-GSN interactionDCLK1 isoform 4-plasma gelsolin interactionDCLK1-GSN PPI

Inhibition of the protein-protein interaction between DCLK1 isoform 4 and plasma gelsolin to suppress non-kinase oncogenic signaling