The DNAJC5 Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the DNAJC5 gene has been disrupted in the human gastric carcinoma line HGC-27. This mixed population provides a loss-of-function model to study cysteine string protein alpha (CSP??), avoiding clonal biases while enabling robust target gene disruption. The product is suited for target validation, pathway dissection, and drug screening applications.
HGC-27 cells were isolated from a metastatic lymph node of a human gastric adenocarcinoma (undifferentiated type) and are extensively used as a model for gastric cancer progression, drug resistance, and metastasis. The cell background endogenously expresses the exocytic and vesicle trafficking machinery, making it permissive for functional characterization of CSP?? in a carcinoma context.
DNAJC5 encodes CSP??, a co-chaperone that cooperates with Hsc70 (HSPA8) to facilitate SNARE complex assembly. CSP?? directly interacts with SNARE proteins STX1A (syntaxin-1), SNAP25, and VAMP2, and functionally couples to voltage-gated Ca2+ channels and clathrin. Upstream regulators include Hsc70, synaptic activity, and cellular stress signals; downstream, CSP?? promotes SNARE-mediated vesicle exocytosis and lysosomal secretion. Disruption of DNAJC5 eliminates CSP?? co-chaperone activity, impairing SNARE complex formation and synaptic-like vesicle exocytosis, thereby perturbing lysosomal function and cellular homeostasis.
In the HGC-27 gastric cancer system, CSP?? loss may specifically alter secretory and lysosomal pathways dependent on SNARE-mediated fusion. Given the role of exocytosis in cancer cell invasion and therapy resistance, this knockout model offers a tool to dissect CSP????s contribution to gastric cancer pathogenesis. Moreover, DNAJC5 mutations are linked to neuronal ceroid lipofuscinosis (Kufs disease) and Parkinson??s disease, so these cells provide a non-neuronal platform to examine conserved neuroprotective and lysosomal dysregulation mechanisms.
Typical assays for characterizing this product include Western blotting for CSP??, RT-qPCR for DNAJC5 expression, immunofluorescence for synaptic vesicle markers, and co-immunoprecipitation for Hsc70 interaction. Functional studies may involve SNARE complex assembly assays, lysosomal function tests, cell viability, and migration/invasion analyses. The knockout model supports investigations into synaptic-like vesicle trafficking in non-neuronal cells, lysosomal storage disorders, secretory pathway alterations in gastric cancer, and drug discovery for neurodegeneration. For further information, please contact Ascent Research.