The HSPA2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated through targeted disruption of the HSPA2 gene in the human NCI-H1975 non-small cell lung cancer cell line. This polyclonal pool provides a heterogeneous loss-of-function model that enables robust assessment of HSPA2-dependent phenotypes while preserving a range of genetic edits and minimizing clonal artifacts.
The NCI-H1975 parental cell line is derived from a human lung adenocarcinoma and represents a well-characterized model of non-small cell lung cancer (NSCLC) with an activating EGFR T790M mutation. It is widely used to study intrinsic and acquired resistance to tyrosine kinase inhibitors, oncogene addiction, and downstream signal transduction in EGFR-mutant NSCLC. Its epithelial origin and genetic background make it particularly suitable for investigating mechanisms of tumor cell survival, migration, and drug response.
HSPA2 encodes an HSP70 family molecular chaperone that facilitates protein folding and maintains proteostasis under stress. It functions as a critical node in pro-survival signaling, primarily through interactions with HSP90 and co-chaperones such as HOP (STIP1) and BAG family members. HSPA2 is transcriptionally activated by HSF1 in response to heat shock, oxidative stress, and oncogenic signals. Downstream, HSPA2 promotes the activation of AKT and ERK1/2 kinases and modulates p53-dependent apoptosis. By forming complexes with client proteins, HSPA2 supports the stabilization of factors essential for proliferation and stress resistance.
In NCI-H1975 cells, HSPA2 contributes to the malignant phenotype by sustaining oncogenic signaling cascades often hyperactive in EGFR-mutant NSCLC. Disruption of HSPA2 is expected to impair stress responses, reduce AKT and ERK pathway activity, and sensitize cells to chemotherapeutics or targeted agents. This knockout model offers a powerful tool for dissecting chaperone-mediated resilience in drug resistance and for identifying synthetic lethal interactions. Moreover, the polyclonal population captures diverse editing outcomes, better reflecting tumor heterogeneity.
This product supports a broad range of applications, including mechanistic studies of stress-induced signaling, apoptosis regulation, and drug resistance. Key assays include western blotting, RT-qPCR, cell viability, colony formation, flow cytometry for apoptosis, migration/invasion assays, and drug sensitivity testing. Co-immunoprecipitation and immunofluorescence enable analysis of protein interactions and localization. For further information, please contact Ascent Research.
