The DNAJC1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population derived from the human lung adenocarcinoma cell line NCI-H1975. This product provides a loss-of-function model for the DNAJC1 gene, generated via CRISPR/Cas9-mediated gene disruption, resulting in a heterogeneous pool of knockout cells. The polyclonal format ensures representation of diverse editing outcomes, enabling robust functional studies without clonal selection artifacts.
The NCI-H1975 cell line is a widely used model of human lung adenocarcinoma, originally established from a non-smoking female patient. These epithelial cells harbor activating mutations in the epidermal growth factor receptor (EGFR), specifically L858R and T790M, which drive oncogenic signaling and confer resistance to first-generation EGFR tyrosine kinase inhibitors. The genetic background of NCI-H1975 makes it particularly relevant for studying EGFR-mutant lung adenocarcinoma biology and therapeutic responses.
DNAJC1 encodes an endoplasmic reticulum (ER)-resident co-chaperone that functions as a critical partner of the major ER chaperone HSPA5 (BiP/GRP78). DNAJC1 interacts directly with BiP and ribosomal complexes at the Sec61 translocon to facilitate co-translational protein folding and maintain ER proteostasis. Under ER stress conditions, DNAJC1 participates in the unfolded protein response (UPR) by modulating BiP activity and attenuating UPR signaling. The UPR sensors ATF6, PERK, and IRE1 (activating XBP1) converge on downstream effectors including ATF4 and CHOP, integrating stress signals to determine cell fate. DNAJC1 also interfaces with ER-associated degradation (ERAD) components such as DERL1 and the VCP/p97 complex, helping to dispose of terminally misfolded proteins. Thus, DNAJC1 is positioned at the nexus of protein folding quality control and stress-adaptive signaling.
In the NCI-H1975 background, DNAJC1 knockout is expected to disrupt ER homeostasis and amplify basal ER stress inherent to cancer cells with high secretory demands. Lung adenocarcinoma cells with gefitinib-resistant EGFR mutations often exhibit heightened UPR activation as a pro-survival mechanism. By impairing DNAJC1 co-chaperone function, this knockout model may sensitize NCI-H1975 cells to ER stress-induced apoptosis and potentially reduce their adaptability to chemotherapeutic insults. This model therefore enables dissection of DNAJC1’s role in maintaining cancer cell viability under oncogenic and therapeutic stress.
Researchers can employ this polyclonal knockout population to investigate DNAJC1-dependent regulation of the UPR and ERAD in lung adenocarcinoma, using techniques such as Western blotting for UPR markers (BiP, CHOP) and RT-qPCR for ER stress-responsive genes. Functional assays including proliferation, apoptosis, and drug sensitivity testing can be combined with RNA-seq to profile transcriptomic changes upon DNAJC1 loss. Co-immunoprecipitation studies with BiP may further elucidate altered chaperone interactions. This model is suitable for mechanistic studies of ER stress resilience, identification of synthetic lethal partners, and preclinical evaluation of therapies targeting proteostasis. For additional technical support or custom projects, please contact Ascent Research.
