The ASRGL1 Knockout LoVo Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the LoVo human colorectal adenocarcinoma cell line. This product provides researchers with a genetically modified pool of cells carrying heterogeneous disruptions in the ASRGL1 gene, creating a robust loss-of-function model for investigating the tumor suppressor functions of ASRGL1 in a colorectal cancer context. The polyclonal format avoids the clonal selection biases inherent in single-cell-derived lines, offering a population that better represents genetic variability often encountered in tumor biology.
The LoVo cell line was originally isolated from a metastatic lymph node of a 56-year-old male patient with colorectal adenocarcinoma and has since been widely adopted as an epithelial model for colorectal cancer research. These cells display typical epithelial morphology and are characterized by their ability to form tumors in xenograft models, making them highly suitable for studies of colorectal tumorigenesis, metastasis, and therapeutic response. The LoVo background is particularly relevant for assessing the impact of ASRGL1 loss on colorectal cancer progression, as this cancer type frequently exhibits alterations in amino acid metabolism and mTOR signaling.
ASRGL1 encodes an enzyme with L-asparaginase and isoaspartyl peptidase activities, hydrolyzing L-asparagine to L-aspartic acid and thereby depleting extracellular asparagine. This function attenuates mTORC1 signaling, a key pathway controlling cell growth and proliferation. Loss of ASRGL1 elevates asparagine levels, driving mTORC1-mediated phosphorylation of S6K and 4E-BP1, and inhibiting apoptosis through reduced caspase-3 cleavage. ASRGL1 expression is induced by endoplasmic reticulum stress via ATF4 and by p53 under nutrient deprivation, and it interacts with ASNS to regulate asparagine homeostasis. Its isoaspartyl peptidase activity also supports protein repair together with PCMT1.
Integrating this ASRGL1 knockout into LoVo cells creates a powerful model for dissecting asparagine metabolism and mTOR signaling in colorectal cancer. Colorectal cancers often display dysregulated mTORC1 activity and altered amino acid utilization, and ASRGL1 is a tumor suppressor in this disease. The polyclonal population mirrors tumor heterogeneity, allowing researchers to examine how asparagine hydrolysis loss reprograms metabolic and proliferative pathways, influences apoptotic thresholds, and modulates sensitivity to amino acid-depleting therapies or mTOR inhibitors.
The cells are designed for functional validation of ASRGL1, mechanistic studies of mTORC1 signaling, and preclinical evaluation of amino acid deprivation strategies. Representative assays include asparaginase activity measurement, MTS/MTT proliferation assays, Western blotting for phospho-S6K and 4E-BP1, caspase-3/7 apoptosis assays, soft agar colony formation, and xenograft tumor growth. They are also a valuable tool for drug discovery targeting asparagine metabolism. For technical support, contact Ascent Research.
