The ASRGL1 Knockout NCI-H1703 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the NCI-H1703 human non-small cell lung cancer cell line, featuring targeted disruption of the ASRGL1 gene. This product provides a genetically heterogeneous pool of edited cells, enabling functional studies of ASRGL1 in a physiologically relevant tumor model without the limitations of monoclonal selection. It is optimized for in vitro applications requiring loss-of-function analysis of asparaginase activity.
The host NCI-H1703 cell line is an epithelial model of human lung squamous cell carcinoma, isolated from a metastatic site and characterized by tumorigenic properties. Widely utilized in non-small cell lung cancer research, these cells facilitate investigation of tumor biology, drug responses, and metabolic adaptations. Their adherent morphology and reliable growth characteristics support gene-editing workflows and subsequent phenotypic assays, making them a robust platform for studying cancer metabolism.
ASRGL1 encodes a dual-activity asparaginase and isoaspartyl peptidase that hydrolyzes L-asparagine to aspartate and ammonia. Under nutrient deprivation and ER stress, ASRGL1 is transcriptionally regulated by ATF4. In knockout cells, loss of ASRGL1 leads to intracellular asparagine accumulation, which modulates mTORC1 signaling through downstream effectors such as S6K and IRS1. ASRGL1 functionally interacts with asparagine synthetase (ASNS), creating a homeostatic balance. Thus, ASRGL1 disruption alters amino acid catabolism and mTORC1-driven protein synthesis, linking nutrient sensing to growth control.
In the context of NCI-H1703 squamous cell carcinoma, ASRGL1 knockout provides a valuable tool to dissect metabolic dependencies. Elevated asparagine levels can desensitize cells to L-asparaginase-based therapies and contribute to chemoresistance, mirroring observations in lung and ovarian cancers. By perturbing mTORC1/S6K signaling, this knockout model helps elucidate how amino acid metabolism interfaces with oncogenic pathways to support tumor proliferation and survival, making it a relevant system for studying NSCLC progression and therapeutic vulnerability.
Key applications encompass amino acid metabolism studies in cancer, chemoresistance mechanisms, identification of metabolic vulnerabilities in NSCLC, and evaluation of asparaginase-based treatments. Compatible assays include western blotting or RT-qPCR for ASRGL1 verification, LC-MS-based amino acid profiling, cell proliferation assays, L-asparaginase sensitivity testing, and phospho-S6 analysis for mTORC1 activity. This polyclonal knockout cell population offers a genetically defined yet heterogeneous system for high-throughput screening and functional genomics. For further information, please contact Ascent Research.
