The CCDC91 Knockout HGC-27 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population targeting the CCDC91 gene in the HGC-27 human gastric carcinoma cell line. This loss-of-function model disrupts CCDC91, a coiled-coil domain-containing protein critical for endosomal sorting and retromer-mediated intracellular trafficking. The CCDC91 protein governs the lysosomal degradation of transmembrane cargoes, including the epidermal growth factor receptor (EGFR), thereby influencing key signaling cascades. The polyclonal format provides a heterogeneous population of edited cells, enabling researchers to study gene disruption effects within a mixed genetic background. This product is designed for rigorous investigation of endosomal trafficking, receptor degradation, and gastric adenocarcinoma biology.
Host HGC-27 cells are a widely utilized gastric adenocarcinoma epithelial cell line derived from the lymph node metastasis of a poorly differentiated gastric carcinoma. These cells retain epithelial morphology and exhibit hallmark features of metastatic gastric cancer, including aggressive growth and altered signaling networks. The HGC-27 background is particularly suited for examining EGFR-driven pathways, as these cells are responsive to EGF stimulation and rely on receptor tyrosine kinase signaling for proliferation and survival. The metastatic origin of HGC-27 makes it a relevant model for studying advanced gastric cancer progression and metastasis-associated trafficking alterations.
CCDC91 functions as a key adaptor in the retromer complex, interacting with VPS35 and VPS26 to orchestrate endosome-to-Golgi retrieval and lysosomal targeting of internalized receptors. It is transcriptionally regulated by GCNF (NR6A1) and responsive to EGF stimulation. Disruption impairs retromer-mediated retrograde transport, causing defective sorting and accumulation of cargoes like EGFR in endosomes. Additional components, including SNX1, SNX2, RAB7A, and LAMP1, participate in these processes. CCDC91 knockout attenuates EGFR degradation, prolonging receptor signaling and affecting downstream cell growth and survival effectors.
In the HGC-27 gastric adenocarcinoma context, CCDC91 loss recapitulates key aspects of aberrant endolysosomal trafficking observed in cancer. Impaired EGFR degradation due to CCDC91 disruption leads to sustained downstream signaling, potentially contributing to oncogenic phenotypes such as enhanced proliferation, apoptosis resistance, and chemoresistance. This polyclonal knockout system allows dissection of CCDC91-dependent trafficking mechanisms without the confounding influences of clonal selection, preserving the inherent heterogeneity of cancer cell populations. It serves as a valuable platform for investigating how endosomal pathway alterations drive gastric cancer aggressiveness and for identifying vulnerabilities associated with retromer dysfunction.
Applications include gastric cancer biology, endosomal trafficking dynamics, drug resistance mechanisms, and EGFR signaling pathway dissection. Researchers can perform western blotting for total and phospho-EGFR, immunofluorescence co-localization of EGFR with LAMP1, endocytosis assays, cell proliferation analyses, flow cytometry-based apoptosis detection, RT-qPCR profiling of autophagy markers, and lysosomal degradation assays. These approaches interrogate CCDC91-mediated trafficking and its impact on receptor fate and cellular responses. For further information, please contact Ascent Research.
