The ITGA4 Knockout HCT 116 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population derived from HCT 116 colorectal carcinoma cells, featuring targeted disruption of the ITGA4 gene. This heterogeneous knockout model enables functional studies of integrin ??4 in a cancer-relevant context. The polyclonal format preserves genetic diversity while creating a loss-of-function system for downstream analyses without clonal isolation biases.
The host HCT 116 cell line is a human colorectal carcinoma epithelial model derived from a male patient, featuring KRAS and PIK3CA mutations with wild-type TP53. This genetic profile makes it a valuable system for investigating colorectal cancer signaling, drug resistance, and metastasis. The cells display integrin-dependent adhesion and motility, and ablating ITGA4 permits detailed analysis of ??4-integrin’s role in tumor cell behavior, including interactions with the extracellular matrix and immune components.
ITGA4 encodes integrin subunit ??4, which heterodimerizes with ITGB1 or ITGB7 to form VLA-4 (??4??1) or ??4??7 receptors. These bind VCAM-1 and fibronectin, activating downstream FAK (PTK2), Src family kinases, PI3K-Akt, and ERK1/2 (MAPK3/MAPK1) pathways. Signaling is regulated by TNF-??, IL-1??, and CXCL12 via CXCR4, which can stimulate NF-??B and AP-1 transcription factors. Additional interaction partners include paxillin, talin-1, and kindlin-3, which modulate adhesion dynamics. Loss of ITGA4 disrupts these networks, impairing cell attachment, spreading, and migration.
In HCT 116 cells, ITGA4 knockout abrogates VLA-4-mediated adhesion and signaling, reducing metastatic potential and altering tumor microenvironment engagement. Given the concurrent KRAS and PIK3CA mutations, this model is ideal for studying crosstalk between integrin and oncogenic pathways. The disruption may affect cell survival, proliferation, and migration, providing insights into colorectal cancer progression and potential therapeutic targets related to cell adhesion and immune cell trafficking. This system is particularly relevant for assessing how integrin ??4 contributes to chemoresistance and invasive behavior in a genetically defined background.
These polyclonal knockout cells are suitable for diverse applications, including cancer metastasis research, cell adhesion studies, and drug resistance mechanism investigations. They can be employed in transwell migration and invasion assays, phospho-FAK ELISA for signaling assessment, western blotting for protein validation, flow cytometry for integrin profiling, and RNA-seq for global gene expression analysis. The polyclonal format ensures functional diversity is captured, avoiding clonal artifacts. For further details or to discuss collaborative projects, please reach out to Ascent Research.
