The ITGA2 Knockout NCI-H1975 Polyclonal Cells product provides a CRISPR/Cas9-mediated loss-of-function model for the integrin subunit alpha-2 (ITGA2) gene in a human non-small cell lung carcinoma (NSCLC) background. This polyclonal knockout cell population, derived from the NCI-H1975 cell line, enables dissection of ITGA2-dependent signaling networks without selecting for a single clonal genotype, maintaining population-level heterogeneity that may better recapitulate tumor complexity. The targeted disruption of ITGA2 abrogates the formation of the collagen-binding VLA-2 (??2??1) integrin heterodimer, allowing researchers to interrogate the role of this adhesion receptor in oncogenic processes such as migration, invasion, and metastasis.
The host cell line, NCI-H1975, originates from the pleural effusion of a female patient with lung adenocarcinoma and harbors well-characterized activating mutations in the epidermal growth factor receptor (EGFR) gene (L858R and T790M) while retaining wild-type TP53. As an established model of EGFR-mutant NSCLC, these cells exhibit constitutive signaling through survival and proliferative pathways, rendering them suitable for investigating integrin-mediated cross-talk with oncogenic drivers. The epithelial origin and metastatic derivation of NCI-H1975 further underscore its relevance for studies on tumor dissemination and extracellular matrix interactions.
ITGA2 encodes the alpha-2 subunit that partners exclusively with ITGB1 to form the VLA-2 collagen receptor. Upon collagen I/IV binding, VLA-2 activates FAK and Src, initiating PI3K/Akt and Ras/Raf/MEK/ERK cascades. These pathways converge on Rho GTPases Rac1, Cdc42, and RhoA to regulate cytoskeletal remodeling and transcriptional upregulation of MMP2, MMP9, and cyclin D1, promoting migration and invasion. Upstream regulators include TGF-??1, TNF-??, IL-1?? via transcription factors Sp1, AP-1, NF-??B, and microRNAs miR-128 and miR-135b. VLA-2 also cooperates with DDR1, talin, vinculin, and paxillin to stabilize focal adhesions.
In NCI-H1975 cells with EGFR L858R/T790M mutations, ITGA2 knockout removes a collagen-sensing mechanism that may cooperate with oncogenic signaling. ITGA2-mediated adhesion can confer resistance to EGFR inhibitors by activating FAK/Akt survival pathways. This polyclonal knockout model thus enables study of integrin ??2 in drug tolerance, EMT, and metastasis. The polyclonal nature may better capture tumor cell adaptation after adhesion receptor loss.
These ITGA2 knockout cells are suited for metastasis, adhesion, drug resistance, and EMT studies, supporting assays such as western blotting, RT-qPCR, Sanger sequencing, flow cytometry, adhesion and invasion assays, immunofluorescence, collagen gel contraction, and phospho-FAK ELISA. In vivo metastasis modeling can further evaluate ITGA2 as a target. Contact Ascent Research for technical details.
