The CC2D1A Knockout HGC-27 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal cell population engineered to disrupt the CC2D1A gene in the HGC-27 human gastric carcinoma cell line. This loss-of-function model enables the study of CC2D1A-dependent regulatory mechanisms without clonal selection, preserving population-level heterogeneity reflective of tumor cell diversity. The targeted gene disruption abrogates expression of the CC2D1A scaffold protein, providing a robust system to investigate its roles in signal transduction and membrane trafficking within a gastric adenocarcinoma context.
HGC-27 cells originate from a poorly differentiated gastric adenocarcinoma metastatic to lymph node, representing an aggressive and clinically relevant model for gastric cancer research. These cells exhibit characteristics of advanced disease, including rapid proliferation and invasive potential, making them suitable for dissecting molecular pathways driving tumor progression. The parental line serves as a well-characterized background for genetic modification, allowing direct comparison between CC2D1A-proficient and -deficient states to assess gene function in malignancy-associated processes.
CC2D1A functions as a scaffold protein critically involved in the negative regulation of NF-??B signaling and endocytic recycling. Mechanistically, it interacts with key components of the I??B kinase (IKK) complex, including IKK-??, IKK-??, and the regulatory subunit NEMO, to restrain NF-??B activation. Upon stimulation by upstream regulators such as TNF-??, IL-1??, Toll-like receptor ligands, and growth factors, loss of CC2D1A leads to enhanced phosphorylation and degradation of I??B??, promoting nuclear translocation of the p65 transcription factor and transcriptional upregulation of NF-??B target genes like IL-6, IL-8, and BIRC3. Additionally, CC2D1A binds Rab4, CHMP4B, CIN85, and phosphatidylinositol 3-phosphate, coupling NF-??B modulation to endosomal trafficking and receptor recycling pathways.
In the HGC-27 gastric cancer setting, CC2D1A disruption is expected to amplify pro-inflammatory and pro-survival NF-??B transcriptional programs while altering endocytic trafficking dynamics. This dual impact may contribute to enhanced therapeutic resistance, increased invasive and metastatic capacity, and dysregulated cellular responses to microenvironmental cues. The model thus provides a physiologically relevant platform to dissect CC2D1A’s tumor-suppressive functions and its intersection with oncogenic signaling networks frequently activated in gastric adenocarcinoma, including those driven by chronic inflammation.
Key research applications include mechanistic studies of NF-??B hyperactivation in gastric cancer, investigation of endosomal recycling defects affecting growth factor receptor trafficking, and functional assays addressing tumor cell invasion, migration, and drug susceptibility. Representative experimental approaches using these polyclonal knockout cells encompass Western blotting and RT-qPCR for NF-??B target gene expression, NF-??B luciferase reporter assays, immunofluorescence imaging of p65 nuclear localization, flow cytometry-based apoptosis and proliferation analyses, Transwell migration/invasion assays, co-immunoprecipitation of CC2D1A-interacting partners, and endocytosis assays to track receptor internalization. For further information, please contact Ascent Research.
