The GULP1 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited pool of polyclonal knockout cells derived from the human non-small cell lung adenocarcinoma cell line NCI-H1975, with targeted disruption of the GULP1 gene. This polyclonal population enables loss-of-function studies of GULP1 in a heterogeneous background, preserving biological variability while avoiding clonal artifacts. The product is supplied as a stable, ready-to-use pool suitable for a broad range of functional assays and genetic screens.
The NCI-H1975 cell line is a well-characterized epithelial model established from a female never-smoker with lung adenocarcinoma. These cells harbor activating mutations in the epidermal growth factor receptor (EGFR), namely L858R and the acquired T790M gatekeeper mutation, conferring sensitivity to first-generation tyrosine kinase inhibitors (TKIs) and representing a critical platform for investigating mechanisms of TKI resistance. The line is widely employed to study EGFR-driven oncogenic signaling, apoptosis evasion, and epithelial?Cmesenchymal transition in the context of therapeutic resistance.
GULP1 (engulfment adaptor PTB domain containing 1) functions as a key adaptor in the phosphatidylserine-mediated engulfment pathway, coupling recognition receptors such as stabilin-2 (STAB2) to downstream cytoskeletal rearrangements and phagosome processing. Upon ligand engagement, GULP1 interacts with ELMO1 and PLSCR1 and activates the small GTPase Rac1, promoting actin reorganization essential for particle internalization. Additionally, GULP1-dependent signaling upregulates ABCA1, facilitating cholesterol efflux and phagosome maturation. Upstream, GULP1 recruitment is regulated by phosphatidylserine exposure on apoptotic cells, integrin ??v??5, TIM-4, and EGFR signaling. Thus, GULP1 integrates signals from diverse surface receptors to coordinate efficient clearance of apoptotic cells and debris.
In the NCI-H1975 adenocarcinoma model, disruption of GULP1 expression impairs the engulfment machinery, potentially leading to accumulation of uncleared apoptotic cells within the tumor microenvironment. This defect may alter inflammatory cytokine profiles, immune surveillance, and drug sensitivity via crosstalk with EGFR signaling pathways. Given the role of phagocytosis in tumor progression and metastasis, GULP1 knockout cells serve as a powerful tool to dissect how apoptotic cell clearance influences EGFR-mutant lung adenocarcinoma biology and TKI resistance. The polyclonal nature of the knockout pool recapitulates the genetic heterogeneity observed in clinical tumors, enhancing translational relevance.
Researchers can utilize these GULP1 knockout polyclonal cells to perform detailed functional studies, including phagocytosis assays with fluorescent apoptotic targets to quantify engulfment efficiency, wound healing migration assays to assess metastatic potential, and co-immunoprecipitation to map protein interaction networks. Western blotting and RT-qPCR enable confirmation of GULP1 disruption and assessment of downstream targets such as Rac1 and ABCA1. Moreover, cell viability assays coupled with EGFR inhibitor treatments (e.g., osimertinib) allow interrogation of GULP1??s role in TKI sensitivity. These cells are also suitable for high-content screening of engulfment-enhancing compounds. For further information or custom requirements, please contact Ascent Research.
