The CCNY Knockout HGC-27 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout population of the HGC-27 human gastric adenocarcinoma cell line, engineered for constitutive disruption of the CCNY (cyclin Y) gene. The polyclonal format yields a heterogeneous pool of knockout cells, avoiding the bottleneck of single-cell cloning and better reflecting population-level gene perturbation effects.
HGC-27 cells were originally derived from a lymph node metastasis of a gastric carcinoma and are characterized by an aggressive, epithelial phenotype with robust Wnt/??-catenin pathway activity. This cell line serves as a well-established model for studying the molecular mechanisms underlying gastric cancer proliferation, invasion, and metastasis, as well as for evaluating targeted therapeutic strategies.
CCNY functions as a non-canonical cyclin that partners with the cyclin-dependent kinases CDK14 (PFTK1) and CDK16 (PCTK1). In the Wnt signaling cascade, the WNT3A ligand stimulates Frizzled/LRP6 receptors, leading to Dishevelled (DVL)-dependent activation of the CCNY?CCDK14/16 complex, which directly phosphorylates LRP6 at Ser1490. This phosphorylation event stabilizes ??-catenin, enabling its nuclear translocation and interaction with TCF/LEF transcription factors to induce expression of proliferation-associated genes including MYC and CCND1. Moreover, CCNY contributes to G2/M cell cycle transition by regulating CDC25 and CDK1. CCNY expression itself is positively modulated by ??-catenin/TCF and by upstream growth factor signals such as EGF and FGF, forming a reinforcing loop that sustains oncogenic signaling.
CRISPR/Cas9-mediated disruption of CCNY in HGC-27 cells abrogates LRP6 phosphorylation, attenuates ??-catenin-dependent transcription, and impedes G2/M progression. Consequently, CCNY knockout cells exhibit diminished proliferative capacity and likely reduced tumorigenicity. Given the dependency of metastatic gastric cancer on Wnt pathway hyperactivation, CCNY-deficient cells serve as a valuable model to explore pathway dependencies, drug sensitivity to Wnt inhibitors, and the development of resistance mechanisms.
This polyclonal knockout model supports diverse experimental applications including Wnt/??-catenin signal transduction studies, cell cycle checkpoint analysis, and functional investigation of gastric cancer biology. Standard assays include western blotting and RT-qPCR for expression analysis, flow cytometry for cell cycle profiling, immunofluorescence to assess ??-catenin localization, TOP/FOP Flash luciferase reporter assays for measuring TCF/LEF transcriptional activity, and co-immunoprecipitation to verify CCNY?CCDK14 complex formation. Additional functional tests such as migration and invasion assays can evaluate metastatic potential, while drug sensitivity screens with Wnt pathway inhibitors address therapeutic response. For further details, please contact Ascent Research.
