The DNAJC1 Knockout AGS Polyclonal Cells represent a heterogeneous polyclonal population of AGS human gastric adenocarcinoma cells genetically modified using CRISPR/Cas9 technology to disrupt the DNAJC1 gene. This product provides a ready-to-use knockout model for studying loss-of-function effects in an epithelial background, without requiring researchers to perform their own gene editing. The polyclonal format ensures representation of diverse editing events across the cell population, offering a robust tool for functional genomics and pathway analysis in gastric cancer research.
AGS cells are a well-characterized human gastric adenocarcinoma cell line derived from a female patient. They exhibit an epithelial morphology and are widely employed as an in vitro model system for gastric cancer biology, including investigations of tumor cell signaling, drug response, and the molecular mechanisms underlying gastric carcinogenesis. Their genetic background, which includes mutations in key tumor suppressor genes such as TP53, renders them suitable for studying the interplay between oncogenic signaling and cellular stress responses.
DNAJC1 encodes an endoplasmic reticulum (ER)-localized DnaJ domain-containing co-chaperone that functions as a critical partner of the HSP70 chaperone BiP/GRP78 (HSPA5). DNAJC1 facilitates BiP-mediated protein folding and directs terminally misfolded proteins toward ER-associated degradation (ERAD) via interactions with the ERAD machinery, including components such as HRD1 and SEL1L. Under conditions of ER stress, the unfolded protein response (UPR) is activated through the coordinated action of upstream sensors IRE1??, PERK, and ATF6. These sensors regulate transcription factors XBP1, ATF4, and ATF6, which in turn govern the expression of downstream targets including BiP, CHOP, and ERAD components. DNAJC1 operates downstream of these UPR sensors, participating in the execution of adaptive programs that restore ER homeostasis. Disruption of DNAJC1 is predicted to compromise protein folding capacity and ERAD efficiency, leading to accumulation of misfolded proteins and altered UPR signaling dynamics.
In AGS gastric cancer cells, knockout of DNAJC1 provides a valuable model system for dissecting the role of ER proteostasis in gastric adenocarcinoma pathogenesis. Given the dependency of rapidly proliferating cancer cells on robust protein folding and secretion pathways, impaired DNAJC1 function may render cells more susceptible to ER stress-induced apoptosis. This model thus enables investigation of how defects in co-chaperone activity influence tumor cell viability, secretory capacity, and sensitivity to pharmacological ER stressors such as tunicamycin and thapsigargin. It also offers a platform for studying the crosstalk between UPR signaling and other pathways relevant to gastric cancer progression.
Researchers can utilize these polyclonal knockout AGS cells in a variety of experimental approaches to examine ER stress biology in gastric cancer. Typical applications include functional studies of the UPR and ERAD, screening for small molecules that modulate ER stress responses, and assessing the impact of DNAJC1 loss on protein secretion and homeostasis. Downstream assays may involve western blotting for UPR markers (BiP, CHOP, XBP1s), RT-qPCR analysis of target gene expression, ER stress reporter assays, apoptosis detection by Annexin V staining, and cell viability measurements following treatment with ER stress-inducing agents. Immunofluorescence microscopy can further reveal ER morphological alterations. This product is a versatile resource for advancing understanding of chaperone functions in cancer. For more information, please contact Ascent Research.
