DST Knockout HGC-27 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HGC-27 human gastric carcinoma cell line, engineered for targeted disruption of the DST gene. This knockout model provides a mixed population of cells with heterogeneous genetic modifications at the DST locus, offering a versatile tool for studying gene function without clonal selection artifacts. The polyclonal format enables the analysis of diverse mutation spectra, better representing the genetic variability encountered in tumor biology.
The parental HGC-27 cell line originates from the lymph node metastasis of a poorly differentiated human gastric adenocarcinoma, displaying adherent epithelial morphology and aggressive metastatic characteristics. As a widely used model for metastatic gastric cancer, HGC-27 retains key features of the tumor microenvironment, making it a relevant system for investigating molecular mechanisms driving invasion and dissemination.
DST encodes dystonin, a large cytoskeletal linker protein also known as bullous pemphigoid antigen 1 (BPAG1), which integrates intermediate filaments, actin microfilaments, and microtubules to maintain cellular structural integrity. Dystonin interacts with hemidesmosomal components such as COL17A1, integrin ??6??4, and plectin, as well as keratins KRT5 and KRT14, and the adaptor protein ERBIN. Upstream, DST expression is regulated by integrin-mediated adhesion, mechanical stress, and growth factor signaling. Downstream, dystonin organizes actin filament networks, anchors keratin intermediate filaments, and stabilizes microtubules, while also influencing cell migration machinery. In signaling terms, it serves as a critical node linking integrin/FAK/SRC pathways with Rho GTPase-mediated cytoskeletal dynamics, thereby coordinating focal adhesion turnover and hemidesmosome stability.
Disruption of DST in HGC-27 polyclonal knockout cells is anticipated to compromise hemidesmosome assembly and focal adhesion integrity, potentially leading to enhanced migratory and invasive phenotypes characteristic of metastatic progression. Given the association of DST variants with epidermolysis bullosa simplex and hereditary sensory and autonomic neuropathy type VI, this model also provides insights into epithelial fragility and mechanotransduction. In the gastric cancer context, loss of dystonin function may recapitulate aspects of tumor cell detachment and dissemination, allowing researchers to dissect the contribution of cytoskeletal cross-talk to peritoneal metastasis.
This polyclonal knockout cell pool is suited for a range of functional assays, including Western blotting to assess remaining dystonin isoforms, immunofluorescence imaging of keratin and actin networks, scratch wound healing assays, and Transwell invasion experiments. Additional applications include cell-extracellular matrix adhesion tests, co-immunoprecipitation of dystonin with its binding partners, transcriptome profiling by RNA-seq, and drug sensitivity screens targeting adhesion-related pathways. Researchers can employ these cells to validate dystonin as a target for restoring cell adhesion in carcinoma, investigate hemidesmosome dynamics, and explore the interplay between mechanical signaling and the cytoskeleton. For further details or to request a quote, please contact Ascent Research.
