The CASP6 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with disruption of the CASP6 gene, providing a loss-of-function model. This heterogeneous pool of edited cells enables study of caspase-6 deficiency in a lung adenocarcinoma background. Generated by non-clonal editing, the polyclonal format is ideal for bulk functional assays and pooled screens, eliminating the need for in-house gene editing. Live cells are delivered ready for expansion and assay deployment.
NCI-H1975 is a non-small cell lung carcinoma (NSCLC) line from a female non-smoker with adenocarcinoma, harboring EGFR L858R/T790M and TP53 mutations. It serves as a model for EGFR-driven tumorigenesis and acquired TKI resistance, making it highly relevant for studying apoptosis signaling and therapeutic vulnerabilities. The CASP6 knockout in this genetic context allows precise dissection of apoptosis execution pathways.
CASP6 is an effector caspase activated by caspase-8 and caspase-9, cleaving nuclear lamins (Lamin A/C), cytoskeletal proteins (??-Fodrin, Cytokeratin 18), and disease-related substrates (Huntingtin, Tau). It mediates apoptotic demolition and participates in PARP and ICAD cleavage, linking to DNA fragmentation. Regulated by Granzyme B, p53, and interacting with XIAP and Hsp90, CASP6 sits at a critical convergence of cell death and protein clearance pathways.
In NCI-H1975, CASP6 disruption impairs both intrinsic and extrinsic apoptosis, likely conferring resistance to chemotherapeutics and EGFR inhibitors. The EGFR T790M background allows investigation of caspase-6’s role in apoptosis evasion and drug resistance. Moreover, the p53 mutation provides a context to study how caspase-6 function is modulated in p53-compromised tumors, potentially impacting nuclear lamina integrity and therapeutic response.
Applications include apoptosis resistance screens, drug sensitivity profiling (EGFR inhibitors, cisplatin, TRAIL), substrate cleavage studies, and inflammatory signaling analysis. Key assays: caspase activity assays, Western blotting for Lamin A/C and PARP cleavage, Annexin V/PI flow cytometry, and immunofluorescence for nuclear lamina. The polyclonal format supports high-throughput drug screens and RNA-seq to identify compensatory pathways. For inquiries, contact Ascent Research.
