The DMTN Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human NCI-H1975 lung adenocarcinoma line. This product offers a heterogeneous pool with targeted DMTN disruption, enabling loss-of-function studies in a well-characterized non-small cell lung cancer (NSCLC) model. The polyclonal format preserves genetic diversity for population-level functional analyses.
The parental NCI-H1975 cell line originates from a pleural effusion of a 62-year-old female lung adenocarcinoma patient and carries EGFR L858R and T790M mutations. These mutations drive constitutive signaling and confer resistance to first-generation EGFR inhibitors, making NCI-H1975 a standard model for EGFR-targeted therapy research.
Dematin, encoded by DMTN, is an actin-binding protein that crosslinks actin filaments and links the cytoskeleton to the plasma membrane through associations with spectrin, adducin, tropomodulin, tropomyosin, and band 4.1. It operates downstream of RhoA, Rac1, and Cdc42, which are activated by integrin and EGFR signaling. Dematin regulates actin dynamics, focal adhesion organization, and the function of E-cadherin, FAK, Src, and matrix metalloproteinases, thereby influencing cell adhesion, migration, and epithelial-mesenchymal transition.
In NCI-H1975 cells, DMTN knockout is expected to compromise cortical actin integrity, impair cell-substrate adhesion, and reduce migratory and invasive capabilities. Altered Rho GTPase signaling may also disrupt FAK and Src activation and shift EMT programs, offering a model to study how actin-regulatory proteins intersect with oncogenic EGFR signaling during NSCLC metastasis.
This polyclonal knockout model supports western blot and immunofluorescence analysis of actin and dematin, as well as Boyden chamber migration, invasion, and cell adhesion assays. Proliferation and apoptosis assays, alongside phospho-EGFR immunoblotting, characterize growth and drug?response phenotypes. The cells are ideal for screening DMTN-dependent drug sensitivities and evaluating combined actin?directed and EGFR?targeted therapies. For further information, please contact Ascent Research.
