The ITGA5 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the ITGA5 gene, which encodes integrin alpha?5. This loss?of?function model is provided as a heterogeneous pool of edited cells, avoiding the clonal selection biases inherent in monoclonal isolates and retaining broad genetic and phenotypic diversity. The product serves as a genetically defined tool for dissecting integrin alpha?5-dependent mechanisms in lung adenocarcinoma research.
NCI-H1975 is a human non?small cell lung adenocarcinoma cell line derived from a female patient. These adherent epithelial cells are tumorigenic and harbor both an activating EGFR mutation (L858R) and a secondary T790M gatekeeper mutation, along with a PIK3CA mutation, resulting in constitutive activation of EGFR and PI3K signaling. This genetic background makes NCI-H1975 a widely used model for studying EGFR?targeted therapy resistance and PI3K?driven tumor progression, with robust in vitro growth and xenograft tumorigenicity.
ITGA5 encodes integrin alpha?5, which heterodimerizes with integrin beta?1 (ITGB1) to form the primary fibronectin receptor. Ligand binding triggers focal adhesion kinase (FAK) and Src activation, which propagate signals through the PI3K?AKT?mTOR and MAPK (ERK1/2) pathways, regulating cell adhesion, migration, and survival. ITGA5 expression is transcriptionally controlled by upstream regulators including TGF???, TNF???, SP1, and AP?1, while downstream effectors such as RhoA, MMP2, and MMP9 mediate ECM remodeling and invasion. Key interacting partners??syndecan?4, uPAR, talin, and vinculin??coordinate focal adhesion dynamics and signal amplification.
In the NCI?H1975 context, constitutive oncogenic signals from EGFR and PI3K intersect with integrin?mediated pathways, influencing tumor cell behavior and drug sensitivity. ITGA5 knockout allows researchers to isolate the specific contributions of ??5??1 integrin to adhesion, migration, and invasion under these mutant conditions. The polyclonal format minimizes clonal artifacts, enabling studies of heterogeneous responses and adaptive signaling rewiring upon integrin loss, which are critical for understanding tumor plasticity and metastatic progression.
The ITGA5 Knockout NCI-H1975 Polyclonal Cells support a range of assays, including cell adhesion, migration/invasion, fibronectin binding, phospho?signaling profiling, and anchorage?independent growth. In xenograft models, they facilitate investigation of ??5??1??s role in metastasis. These cells also enable evaluation of integrin?targeted therapeutics and resistance mechanisms in EGFR?mutant lung cancer. Standard characterization by Western blotting, RT?qPCR, and flow cytometry is recommended. For further information, please contact Ascent Research.
