The DNAJB11 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the human gastric adenocarcinoma cell line HGC-27. This product provides a genetically heterogeneous pool with targeted disruption of the DNAJB11 gene, enabling loss-of-function studies without the biases of clonal selection. The polyclonal format reflects the natural diversity of cancer cell populations while ensuring robust knockout representation, making it suitable for pooled functional assays and screens. As a CRISPR/Cas9-mediated gene disruption model, it serves as a versatile tool for investigating DNAJB11-dependent mechanisms in a disease-relevant gastric cancer context.
HGC-27 cells originate from a lymph node metastasis of a patient with gastric adenocarcinoma and are widely employed as a model of advanced gastric carcinoma. These epithelial cancer cells retain key oncogenic pathways and characteristics of tumor progression, providing a relevant background for studying cancer cell biology and therapeutic responses. The cell line??s metastatic origin and cancerous phenotype are especially useful for exploring how endoplasmic reticulum (ER) stress and protein quality control pathways influence aggressive tumor behavior and drug sensitivity.
DNAJB11 encodes an ER luminal co-chaperone that recruits HSPA5 (BiP/GRP78) to misfolded proteins, directing them toward refolding or ER-associated degradation (ERAD). It functions downstream of ER stress sensors PERK, IRE1??, and ATF6, and interacts with ERAD components such as VCP/p97, OS9, and SEL1L to facilitate substrate retro-translocation and proteasomal degradation. Under ER stress, activated transcription factors XBP1, ATF6, and ATF4 upregulate UPR targets including HSPA5 and CHOP. DNAJB11-dependent delivery of clients to the ubiquitin-proteasome system is critical for ER proteostasis. Consequently, its knockout impairs clearance of misfolded proteins, leading to sustained UPR activation and heightened sensitivity to ER stressors like tunicamycin.
In the HGC-27 gastric cancer background, where proteotoxic burden from high secretory demands and genomic instability is common, DNAJB11 knockout provides a system to dissect the reliance of malignant cells on ER protein quality control. Loss of DNAJB11 is expected to enhance UPR signaling and expose vulnerabilities linked to ERAD deficiency, offering insights into tumor cell survival, metastasis, and drug resistance. This model is particularly relevant for studying how gastric adenocarcinoma cells cope with proteotoxic stress, potentially revealing synthetic lethal interactions and novel therapeutic targets.
Research applications include monitoring UPR activation by western blotting for HSPA5 and CHOP, assessing XBP1 splicing via RT-qPCR, and evaluating ER morphology by immunofluorescence. The polyclonal knockout cells are amenable to ER stress reporter assays, proteasome activity measurements, and cell viability screens under ER stress-inducing conditions. This model supports drug discovery efforts targeting ER stress modulators and investigations into the interplay between ERAD and autophagy in cancer. For further information, please contact Ascent Research.
