The HMMR Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited population of NCI-H1975 lung adenocarcinoma cells with targeted disruption of the HMMR (RHAMM) gene. This polyclonal knockout model enables loss-of-function analysis of the hyaluronan receptor in a heterogeneous cell pool, avoiding clonal artifacts. Derived from Homo sapiens, the cells provide a platform for investigating HMMR-driven processes in a cancer-relevant context.
The NCI-H1975 line originates from a non-smoking female with NSCLC adenocarcinoma and carries EGFR L858R and T790M mutations, conferring resistance to first-generation EGFR TKIs. These adherent epithelial cells are a standard model for studying drug resistance and metastasis in lung cancer. The mutant EGFR background renders them suitable for exploring cross-talk between hyaluronan signaling and oncogenic kinase pathways.
HMMR (RHAMM) is a receptor for hyaluronan that regulates cell motility, proliferation, and wound healing by interacting with CD44 and the cytoskeleton. Activation by hyaluronan, EGF, TGF-beta, and PDGF triggers downstream Ras-ERK1/2, PI3K-AKT, and FAK pathways. HMMR collaborates with microtubules and actin via associations with tubulin, TPX2, and Rho GTPases. It promotes Cyclin D1 expression, MMP secretion, and focal adhesion dynamics, driving migration and invasion. The HMMR?CCD44?Chyaluronan complex is a key node in metastasis-associated signaling networks.
In NCI-H1975 cells, HMMR likely potentiates EGFR-driven malignancy by sustaining ERK1/2 and AKT activation. Knocking out HMMR in this polyclonal population is expected to impair cell migration, reduce metastatic potential, and enhance sensitivity to EGFR TKIs. This model therefore enables dissection of mechanisms linking hyaluronan to TKI resistance and tumor microenvironment remodeling. It also facilitates exploration of HMMR as a therapeutic target in EGFR-mutant lung adenocarcinoma.
Researchers can apply this knockout product to investigate cancer metastasis, hyaluronan biology, and drug resistance using assays such as wound healing, transwell migration, and western blotting for phospho-ERK. qPCR and immunofluorescence validate HMMR depletion and localization, while co-immunoprecipitation tests CD44 interaction. Proliferation changes are measurable via MTT assay, and in vivo metastasis models can assess systemic spread. For additional details, contact Ascent Research.
