HPS3 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population from the NCI-H1975 human lung adenocarcinoma epithelial line. CRISPR/Cas9-mediated disruption of HPS3 creates a loss-of-function model for studying lysosome-related organelle biogenesis and Hermansky-Pudlak syndrome type 3 in an EGFR-mutant non-small cell lung cancer background. This heterogeneous pool enables functional assays without single-cell cloning, facilitating investigation of HPS3-dependent pathways.
The parental NCI-H1975 cell line originates from a female patient with non-small cell lung adenocarcinoma, carrying EGFR L858R/T790M mutations and derived from pleural effusion. These epithelial cells model metastatic lung adenocarcinoma, especially EGFR-targeted therapy resistance. The background provides clinically relevant insights into cancer cell biology, including oncogenic EGFR signaling and its crosstalk with lysosomal trafficking.
HPS3 encodes a BLOC-2 subunit that interacts with HPS5 and HPS6 to regulate cargo transport to lysosome-related organelles, essential for melanosome and platelet dense granule biogenesis and endosomal trafficking. Upstream, TFEB, TFE3, and MITF, activated by ??-MSH/MC1R/cAMP, modulate HPS3 activity. BLOC-2 partners with Rab32 and Rab38, and AP-3, to direct tyrosinase and TYRP1 to melanosomes. Downstream, HPS3-dependent trafficking ensures localization of lysosomal hydrolases, VAMP7, and STX13, supporting lysosomal exocytosis and secretion of platelet dense granule contents like serotonin and ATP.
In the NCI-H1975 adenocarcinoma background, HPS3 knockout disrupts BLOC-2, impairing lysosome-related organelle functions linked to cancer progression. Lysosomal biogenesis and trafficking influence EGFR-mutant cell survival, autophagy, and metastasis. Loss of HPS3 may alter lysosomal enzyme secretion and surfactant protein trafficking, providing a platform to study organelle defects in lung adenocarcinoma pathophysiology. This model also helps elucidate HPS3 contributions to Hermansky-Pudlak syndrome type 3-related platelet defects and pulmonary fibrosis in an epithelial cancer context.
This polyclonal knockout cell population is ideal for investigating lysosome-related organelle biogenesis, Hermansky-Pudlak syndrome type 3 modeling, and platelet dense granule research. It enables study of EGFR-mutant cancer cell biology and the interplay between oncogenic signaling and lysosomal function. Representative assays include western blotting, immunofluorescence, transmission electron microscopy, RT-qPCR, lysosomal exocytosis assays, cell migration assays, and drug sensitivity testing with EGFR inhibitors. For additional information, contact Ascent Research.
