The ITGB6 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 human lung adenocarcinoma cell line. These cells feature disruption of the ITGB6 gene, which encodes integrin ??6, via CRISPR/Cas9-mediated targeting. The polyclonal pool comprises a heterogeneous collection of edited alleles, providing a robust loss-of-function model for studying ITGB6-dependent processes in a disease-relevant context.
The parental NCI-H1975 cell line is a well-characterized model of non-small cell lung adenocarcinoma (NSCLC) isolated from a non-smoking female patient. It harbors activating EGFR L858R and drug-resistance T790M mutations, which underscore its utility in investigating EGFR-targeted therapy resistance and tumor progression. As an adherent epithelial cell line, NCI-H1975 retains key features of lung adenocarcinoma, including dysregulated proliferative signaling and metastatic potential, making it a suitable host for interrogating the role of integrin ??6 in this molecular context.
ITGB6 encodes the integrin ??6 subunit, which pairs with integrin ??V (ITGAV) to form the ??V??6 heterodimer. This receptor binds RGD-motif ligands, particularly LAP-TGFB1, inducing a conformational change that releases active TGFB1. Activated TGFB1 signals through both SMAD2/3-dependent and non-canonical FAK/SRC/MAPK (ERK1/2) pathways. ITGB6 function is regulated by upstream factors including EGF, TGFB1, and transcription factors ETS1 and HOXA1, and engages downstream effectors such as SMAD2, SMAD3, FAK, SRC, and MAPK3/1. The ??V??6 complex also interacts with fibronectin (FN1) and osteopontin (SPP1), connecting integrin signaling to adhesion, migration, and fibrosis.
In NCI-H1975 NSCLC cells, ITGB6-mediated TGFB1 activation contributes to EMT, drug resistance, and tumor microenvironment modulation. ??V??6 integrin is linked to poor prognosis in lung cancer, and its upregulation may foster a fibrotic and immunosuppressive niche. Disrupting ITGB6 in this EGFR-mutant background allows dissection of integrin ??6-dependent modulation of NSCLC cell behavior, including responses to osimertinib, and exploration of cross-talk between integrin and EGFR signaling pathways that may drive adaptive resistance.
This polyclonal knockout population supports diverse functional and pharmacological assays. Western blotting for ITGB6 and phospho-SMAD2, RT-qPCR for TGFB1 targets, and flow cytometry for surface ??V??6 confirm gene disruption and pathway activity. Cell adhesion to fibronectin, TGF?? bioassays (PAI-1 luciferase), and migration/invasion assays assess integrin function. Co-immunoprecipitation of ??V??6 with LAP-TGFB1 and drug sensitivity profiling (e.g., osimertinib) further expand its utility in fibrosis and cancer research. For additional information or technical support, please contact Ascent Research.
