The IGF2R Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to eliminate IGF2R gene expression in the NCI-H1975 human lung adenocarcinoma cell line. This polyclonal loss-of-function model enables researchers to study the consequences of abolished IGF2R-mediated functions, including lysosomal enzyme trafficking and IGF2 clearance, without the need for single-cell cloning.
NCI-H1975 is an adherent epithelial cell line derived from the pleural effusion of a female patient with non-small cell lung cancer (NSCLC). It harbors activating EGFR mutations (L858R and T790M) and serves as a widely characterized model for EGFR-mutant lung adenocarcinoma, particularly in studies of targeted therapy resistance and tumor progression.
The IGF2R (cation-independent mannose-6-phosphate receptor) is a multifunctional transmembrane protein that directs lysosomal enzymes bearing M6P modifications from the trans-Golgi network to endosomes and mediates the endocytosis and lysosomal degradation of insulin-like growth factor 2 (IGF2). In addition, it activates latent transforming growth factor-beta (TGF-??) and interacts with plasminogen and urokinase receptor (uPAR). Knockout cells abolish these functions, leading to elevated extracellular IGF2, sustained IGF1R?CAKT?CMAPK signaling, and impaired TGF-?? activation and lysosomal biogenesis. Key known interacting factors include M6P-tagged hydrolases, clathrin adaptors, and latent TGF-??, with upstream regulation by SP1, p53, and TGF-?? signaling itself.
In EGFR-mutant NSCLC models, loss of IGF2R phenocopies critical aspects of tumor progression, including enhanced proliferation, survival, and potential resistance to EGFR tyrosine kinase inhibitors such as gefitinib. This polyclonal knockout population allows detailed dissection of IGF2R??s tumor-suppressive roles and its interplay with the oncogenic IGF1R and TGF-?? pathways, linking lysosomal dysfunction to cancer cell signaling.
Researchers can employ these cells in diverse assays, including western blotting for IGF2R, phospho-IGF1R, and AKT; RT-qPCR for downstream targets; ELISA for IGF2 quantification; immunofluorescence for lysosomal markers such as LAMP1; flow cytometry for surface IGF2R; proliferation and migration/invasion assays; and drug sensitivity testing. The model is suitable for studying lysosomal enzyme trafficking defects, IGF2/IGF1R signaling in EGFR-mutant NSCLC, mechanisms of drug resistance, and testing reactivation of tumor-suppressive pathways. For further details, contact Ascent Research.
