The DNAJC1 Knockout HGC-27 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric adenocarcinoma cell line. This product provides a loss-of-function model through CRISPR/Cas9-mediated disruption of the DNAJC1 gene, enabling investigation of DNAJC1??s role in endoplasmic reticulum (ER) proteostasis and stress signaling. The polyclonal population retains genetic heterogeneity, offering a robust tool for studying gene function without the limitations of clonal selection.
HGC-27 cells are a well-characterized epithelial cell line originally isolated from the lymph node metastasis of a human gastric adenocarcinoma. These cells serve as an established in vitro model for gastric adenocarcinoma, exhibiting features relevant to metastatic gastric cancer biology. Their use in knockout studies facilitates the dissection of molecular mechanisms underlying gastric cancer progression and therapeutic resistance.
DNAJC1 encodes an ER-resident J-domain co-chaperone that directly stimulates the ATPase activity of HSPA5 (BiP), a central regulator of ER protein folding and the unfolded protein response (UPR). DNAJC1 interacts with HSPA5, the SEC61 translocon, ribosomes, and ER membrane proteins to facilitate co-translational import and folding. Upstream stress sensors??including IRE1, ATF6, and PERK??activate UPR signaling cascades that converge on transcription factors such as XBP1s, ATF4, and CHOP, while DNAJC1 acts as a key co-chaperone that modulates HSPA5 function under both basal and ER stress conditions. Loss of DNAJC1 disrupts this chaperone network, leading to impaired protein folding capacity and prolonged UPR activation.
In the context of HGC-27 gastric cancer cells, DNAJC1 knockout likely compromises the adaptive ER stress response, sensitizing cells to proteotoxic insults and potentially altering survival pathways crucial for tumor growth and metastasis. Given the heightened ER stress experienced by rapidly proliferating cancer cells, this knockout model enables the study of how DNAJC1-dependent chaperone activity influences gastric cancer cell fitness, migration, and invasion under normal and stressed conditions.
Researchers can employ this polyclonal knockout population to investigate ER stress response mechanisms in gastric cancer using assays such as western blotting for DNAJC1, HSPA5, and UPR markers (CHOP, XBP1s), RT-qPCR for UPR target genes, immunofluorescence for ER morphology, and ER stress induction with tunicamycin or thapsigargin. Additional applications include cell viability and apoptosis assays under ER stress, co-immunoprecipitation to confirm DNAJC1-HSPA5 interaction, proteostasis analysis, and migration/invasion studies. This model is ideally suited for drug screening to identify ER stress modulators and for deciphering the molecular interplay between chaperone networks and oncogenic signaling. For further information, please contact Ascent Research.
