The KIAA1191 Knockout NCI-H1975 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population generated from the NCI-H1975 human lung adenocarcinoma cell line. This product contains a heterogeneous pool of cells with targeted disruptions in the KIAA1191 gene, providing a stable loss-of-function model. The polyclonal format captures diverse editing outcomes, facilitating robust population-level analyses of gene function.
The NCI-H1975 host cell line is an epithelial cell line derived from a lung adenocarcinoma patient. It harbors two clinically relevant mutations in the epidermal growth factor receptor (EGFR) gene: the activating L858R substitution and the T790M gatekeeper mutation, which together confer resistance to first-generation EGFR tyrosine kinase inhibitors such as gefitinib and erlotinib. This cell line is widely employed to study EGFR-driven oncogenic signaling and mechanisms of drug resistance in lung cancer.
KIAA1191, also known as striatin-interacting protein 2 (STRIP2), is a scaffold protein of the STRIPAK complex. It directly interacts with striatin family members (STRN, STRN3, STRN4), protein phosphatase 2A (PP2A) catalytic and regulatory subunits, and MOB kinase activators. By recruiting PP2A to its substrates, KIAA1191 regulates dephosphorylation of key signaling kinases, including MST1/2 in the Hippo pathway and ERK1/2 in the MAPK cascade, thereby controlling YAP/TAZ transcriptional activity and cytoskeletal dynamics.
In the EGFR-mutant genetic background of NCI-H1975 cells, knockout of KIAA1191 is expected to disrupt STRIPAK-mediated PP2A targeting, leading to altered phosphorylation of MST1/2 and ERK1/2. This may result in dysregulated YAP/TAZ-driven proliferation and apoptosis, as well as modified sensitivity to EGFR inhibitors. Consequently, this knockout model enables investigation of scaffold protein functions in the context of oncogenic EGFR signaling and acquired TKI resistance.
This polyclonal knockout cell population supports a broad range of research applications, including functional dissection of the STRIPAK complex, analysis of Hippo and MAPK pathway crosstalk, and evaluation of therapeutic responses in EGFR-mutant lung adenocarcinoma. Researchers can employ assays such as western blotting for phospho-MST1/2 and phospho-ERK1/2, cell proliferation and apoptosis measurements, drug sensitivity testing with osimertinib, and co-immunoprecipitation of STRIPAK components. For additional details, please contact Ascent Research.
