JAK2 Knockout DLD-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the DLD-1 colorectal adenocarcinoma line, designed for loss-of-function studies of JAK2. This polyclonal knockout model disrupts JAK2 expression across the cell pool, enabling robust investigation of JAK2-dependent signaling. The cells are generated via CRISPR/Cas9-mediated gene disruption, offering a versatile tool for studying cytokine receptor signaling and oncogenic pathways in colorectal cancer.
The DLD-1 cell line originates from a male patient with Dukes’ type C colorectal adenocarcinoma and exhibits adherent epithelial morphology. It is a well-established model for colorectal tumor biology, retaining key signaling dependencies including JAK-STAT, PI3K-AKT, and MAPK pathways. This background makes DLD-1 particularly suited for dissecting JAK2 function in colorectal tumorigenesis and therapeutic response.
JAK2 is a non-receptor tyrosine kinase central to cytokine receptor signaling. Upon ligand binding to receptors such as IL-6R, IFNGR, EPOR, or GHR, JAK2 becomes activated and phosphorylates STAT3 and STAT5, triggering their nuclear translocation and transcription of targets like BCL2 and CCND1. JAK2 also activates PI3K-AKT-mTOR and MAPK cascades downstream of gp130 and SRC kinases. The kinase is regulated by SOCS proteins and SHP2 (PTPN11). A representative signaling module is the IL-6/IL-6R/JAK2/STAT3/SOCS3 axis, frequently dysregulated in cancer.
In DLD-1 cells, JAK2 signaling promotes proliferation, survival, and invasion. Knockout of JAK2 abrogates cytokine-induced STAT3/5 phosphorylation and reduces CCND1 and BCL2 expression. This model permits dissection of JAK2 contributions to colorectal cancer, including IL-6-driven progression and therapy resistance. The polyclonal nature avoids clonal bias and more faithfully reflects tumor heterogeneity.
Applications include Western blotting for phospho-JAK2 and phospho-STAT3, RT-qPCR of STAT3 target genes, proliferation (MTT, BrdU) and migration/invasion (Transwell) assays, and annexin V apoptosis detection by flow cytometry. IL-6 stimulation can probe JAK-STAT pathway dynamics. These cells enable studies of cytokine-mediated tumor progression, drug resistance, and functional oncogenic signaling validation, as well as evaluation of JAK2 inhibitor specificity. For further details, contact Ascent Research.
