The GYS1 Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the glycogen synthase 1 (GYS1) gene has been disrupted to create a loss-of-function model. This population provides a powerful tool for investigating the role of glycogen synthesis in lung adenocarcinoma biology. The polyclonal nature ensures a heterogeneous knockout population, avoiding clonal artifacts while enabling robust functional studies.
The NCI-H1975 host cell line is a human lung adenocarcinoma epithelial model derived from a female patient, harboring the activating EGFR mutations L858R and T790M. These mutations are clinically relevant as they confer sensitivity to first-generation EGFR tyrosine kinase inhibitors (e.g., erlotinib) and resistance via the T790M gatekeeper mutation. NCI-H1975 is widely employed to study non-small cell lung cancer (NSCLC) biology, including oncogenic signaling, drug resistance, and metabolic adaptations.
GYS1 encodes muscle glycogen synthase, which catalyzes the rate-limiting step in glycogen synthesis by transferring the glucosyl moiety of UDP-glucose to a growing glycogen chain, a process initiated by glycogenin. GYS1 is activated by insulin signaling through the insulin receptor/IRS1/PI3K/AKT axis, which phosphorylates and inhibits GSK3, relieving GSK3-mediated inhibitory phosphorylation of GYS1. Conversely, PKA phosphorylates GYS1 at distinct sites to inhibit activity, while protein phosphatase 1 (PP1), targeted to glycogen by PPP1R3, dephosphorylates and activates GYS1. AMPK also interacts with the glycogen synthesis machinery, integrating energy status. Downstream, GYS1 determines glycogen accumulation and influences glucose-6-phosphate and UDP-glucose pools, linking to central carbon metabolism and mTOR signaling.
In the NCI-H1975 adenocarcinoma context, GYS1 knockout abrogates glycogen synthesis, disrupting cellular energy storage and potentially altering metabolic reprogramming associated with EGFR-driven oncogenesis. Glycogen metabolism has been implicated in cancer cell survival under hypoxic and nutrient-deprived conditions, as well as in the development of drug resistance. Thus, loss of GYS1 may sensitize cells to metabolic stress, modulate signaling through mTOR, and affect adaptation to hypoxia, providing a model to dissect the contribution of glycogen storage to lung adenocarcinoma progression and therapy response.
This knockout cell population is suitable for a range of mechanistic and translational studies. Applications include investigating metabolic reprogramming in drug-resistant NSCLC, modeling glycogen storage disease type 0, and examining insulin/growth factor signaling crosstalk. Users can quantify glycogen levels via PAS staining or enzymatic assays, assess metabolic flux using Seahorse analyzers, monitor glucose uptake, validate GYS1 loss by western blotting and RT-qPCR, and visualize glycogen with immunofluorescence. For further details or to inquire about ordering, please contact Ascent Research.
