Cluster of differentiation 44 (CD44)-Janus kinase 2 (JAK2)-Signal transducer and activator of transcription 3 (STAT3) signaling axis (CD44-STAT3-JAK2)

The Cluster of differentiation 44 (CD44)-Janus kinase 2 (JAK2)-Signal transducer and activator of transcription 3 (STAT3) signaling axis is a critical molecular pathway that integrates extracellular signals with nuclear gene expression to drive tumor progression and maintain cancer stem cell (CSC) populations [1]. CD44, a transmembrane glycoprotein and primary receptor for hyaluronan, acts as a scaffold that facilitates the recruitment and activation of the non-receptor tyrosine kinase JAK2 [2]. Once activated, JAK2 phosphorylates STAT3, which then dimerizes and translocates to the nucleus to regulate the expression of genes associated with cell survival, proliferation, and the epithelial-mesenchymal transition (EMT) [1, 3]. This axis is frequently overactivated in various malignancies, including breast, gastric, and colorectal cancers, where it contributes to therapeutic resistance and poor clinical outcomes [1, 2]. Therapeutic strategies targeting this axis include small-molecule inhibitors of JAK2 and STAT3, as well as monoclonal antibodies directed against CD44, aimed at disrupting the survival signals of CSCs [4, 5].

Other names

CD44/JAK2/STAT3 pathwayCD44-JAK2-STAT3 axisCD44-mediated JAK2/STAT3 signaling

Inhibition of JAK2-mediated phosphorylation of STAT3, blockade of CD44-ligand binding, and direct inhibition of STAT3 transcriptional activity [1, 2, 4].