The ITGB1 Knockout NCI-H1975 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human non-small cell lung adenocarcinoma cell line, in which the ITGB1 gene has been disrupted. This polyclonal knockout pool offers a heterogeneous loss-of-function model for studying integrin ??1-dependent cellular processes, without the clonal selection steps that can introduce confounding genetic drift. The use of CRISPR/Cas9-mediated gene disruption enables robust ablation of ITGB1 expression across the population, providing a versatile tool for investigating integrin signaling in a cancer-relevant background.
The host cell line, NCI-H1975, is a lung adenocarcinoma model carrying EGFR L858R and T790M mutations. L858R confers sensitivity to first-generation EGFR TKIs, while T790M is a common resistance mutation, making this line pivotal for studying acquired resistance and evaluating next-generation TKIs. This genetic context provides a clinically relevant system for dissecting integrin signaling in EGFR-mutant cancer.
ITGB1 encodes integrin ??1 (CD29), which heterodimerizes with ?? subunits (e.g., ITGA5, ITGAV) to form receptors for ECM proteins such as fibronectin, collagen I, and laminin. Ligand binding induces clustering and recruitment of focal adhesion proteins talin, paxillin, vinculin, and kindlin, linking to the actin cytoskeleton. This activates FAK and Src kinase, leading to downstream PI3K-AKT and RAS-MAPK (ERK1/2) signaling, which promote proliferation, survival, and migration. Integrin ??1 is upregulated by growth factors like TGF-?? and EGF and drives expression of Cyclin D1, MMP2, and Snail, fostering EMT and metastasis. Additionally, RhoA-ROCK signaling downstream of ??1 modulates cytoskeletal dynamics.
In NCI-H1975, ITGB1 knockout disrupts integrin-mediated adhesion, migration, and survival signals that can act in parallel to mutant EGFR. Since ??1 signaling activates PI3K-AKT and ERK, its loss may reduce tumor cell invasion and alter TKI sensitivity, making this model valuable for examining drug-tolerant states and EMT. The polyclonal nature avoids clonal artifacts and ensures robust, reproducible phenotypes.
This product supports diverse applications: adhesion and migration assays (e.g., transwell, ECM adhesion), signaling analysis by Western blot for pFAK and pAKT, and flow cytometry for CD29. It is ideal for drug resistance studies, examining ITGB1??s role in EGFR TKI sensitivity, and EMT research using co-immunoprecipitation to assess integrin complexes. The cells also enable screening of anti-metastatic or integrin-targeted compounds. For further technical information, please contact Ascent Research.
