The GSTK1 Knockout NCI-H1975 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1975 lung adenocarcinoma line, providing a heterogeneous pool of cells with targeted disruption of the GSTK1 gene. This format enables robust assessment of loss-of-function phenotypes without the biases of single-cell cloning.
NCI-H1975 is an adherent epithelial cell line established from the pleural effusion of a non-smoking female with lung adenocarcinoma. It harbors EGFR L858R and T790M mutations, representing a widely used model for EGFR-targeted therapy resistance and oncogenic signaling. The cell line??s clinically relevant background makes it an appropriate host for studying redox biology and drug response.
GSTK1 encodes a mitochondrial glutathione S-transferase/peroxidase that catalyzes the conjugation of reduced glutathione to lipid hydroperoxides and reactive aldehydes such as 4-hydroxynonenal (4-HNE), thereby detoxifying lipid peroxides and preserving mitochondrial redox homeostasis. This function is critical for inhibiting ferroptosis, a regulated cell death driven by lipid peroxidation. GSTK1 is transcriptionally regulated by the NRF2 (NFE2L2) transcription factor, which is itself controlled by KEAP1-mediated degradation. Under oxidative stress, NRF2 activates GSTK1 together with GPX4 to mount a coordinated defense against lipid peroxide accumulation. Thus, GSTK1 operates within the NRF2?CKEAP1?Cglutathione axis to suppress ferroptosis and maintain cellular viability.
Disruption of GSTK1 in the NCI-H1975 background is anticipated to increase lipid peroxidation and sensitize cells to ferroptotic triggers such as erastin or RSL3, revealing vulnerabilities in the antioxidant network of lung adenocarcinoma cells. Given the cells?? EGFR-driven oncogenic signaling and intrinsic oxidative burden, this knockout model is valuable for exploring the intersection of growth factor signaling and redox regulation, as well as mechanisms of ferroptosis resistance in drug-tolerant persister cells.
Research applications include ferroptosis studies, oxidative stress biology, chemoresistance investigations, and synthetic lethality screening. Compatible assays encompass lipid peroxidation measurement with C11-BODIPY, cell viability assays, glutathione quantification, colony formation, and molecular validation via western blot and RT-qPCR. For inquiries and ordering, contact Ascent Research.
