The HAVCR1 Knockout HT29 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the HT29 human colorectal adenocarcinoma cell line. These cells harbor a targeted disruption of the HAVCR1 gene, encoding the TIM-1 (T-cell immunoglobulin and mucin domain 1) transmembrane glycoprotein. This polyclonal knockout model provides a genetically heterogeneous pool of edited cells for studying loss-of-function phenotypes in cancer biology, immunology, and signal transduction research.
HT29 is an established epithelial cell line isolated from a primary colon adenocarcinoma of a 44-year-old female. The cells are adherent, tumorigenic in nude mice, and carry well-characterized oncogenic mutations in APC, TP53, and BRAF (V600E), while retaining wild-type KRAS. HT29 is widely employed as a model for intestinal epithelial biology, differentiation, mucin production, and colon adenocarcinoma signaling, making it a relevant platform for interrogating gene function in colorectal tumorigenesis.
HAVCR1 (TIM-1) functions as a membrane receptor for phosphatidylserine and hepatitis A virus, mediating diverse processes including T-cell co-stimulation, immune tolerance, and clearance of apoptotic cells. Mechanistically, TIM-1 engagement by its ligands, such as phosphatidylserine and TIM-4, recruits Fyn kinase and the PI3K p85 subunit through adaptors like GAB2, leading to AKT phosphorylation and NF-??B activation. This signaling cascade upregulates downstream effectors such as Bcl-2, MMP-9, and IL-4, with regulatory inputs from IL-4/STAT6 and T-cell receptor/NFAT pathways. In epithelial contexts, TIM-1 may additionally influence cell adhesion and migration.
In HT29 colorectal cancer cells, knockout of HAVCR1 is expected to disrupt PI3K/AKT and NF-??B signaling axes that support tumor cell survival, proliferation, and migration. Given the concurrent mutations in APC, TP53, and BRAF(V600E), this model allows dissection of TIM-1??s contribution to oncogenic signaling and crosstalk with the tumor microenvironment. Loss of TIM-1 may impair downstream AKT phosphorylation, reduce MMP-9-mediated invasiveness, and alter immune-modulatory cytokine production, providing insights into TIM-1 as a potential therapeutic target in colorectal cancer.
This knockout cell product is suited for functional studies of HAVCR1 in colorectal cancer progression, including analyses of cell viability (MTT assay), migration and invasion (Transwell assays), apoptosis (Annexin V staining), and phospho-signaling (p-AKT, p-NF??B). It enables investigation of TIM-1-dependent regulation of IL-4 production, Bcl-2 expression, and MMP-9 activity. Additional applications include drug target validation, modeling of phosphatidylserine receptor biology, and hepatitis A virus receptor studies. Standard characterization can be performed via Western blotting and RT-qPCR. For further information, contact Ascent Research.
