The CASZ1 Knockout HGC-27 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population derived from the human gastric adenocarcinoma cell line HGC-27, with targeted disruption of the CASZ1 gene. This heterogeneous pool contains diverse gene-disruption variants, enabling unbiased loss-of-function studies. The CRISPR/Cas9 system introduces modifications at the CASZ1 locus, providing a mixed population for population-level analyses of transcription, signaling, and tumor suppression.
HGC-27 is a human gastric adenocarcinoma cell line originating from lymph node metastasis of an undifferentiated gastric carcinoma. It exhibits rapid proliferation, loss of epithelial markers, and invasive capacity, modeling aggressive metastatic gastric cancer. This cell line is a relevant in vitro system for studying tumor progression, epithelial-mesenchymal transition (EMT), and therapeutic resistance, particularly for exploring the impact of differentiation-associated factors like CASZ1.
CASZ1 encodes a zinc finger transcription factor and tumor suppressor that recruits the NuRD complex (HDAC1, HDAC2, TLE1, REST) to regulate gene expression. It is activated by upstream signals BMP4, Wnt, and Notch; it transcriptionally activates CDKN1A (p21) and CDH1 (E-cadherin), while repressing MYCN and the matrix metalloproteinases MMP2 and MMP9. Through these effectors, CASZ1 integrates input from TGF-beta/Smad (SMAD2/3), Wnt/beta-catenin (CTNNB1), Notch (HES1), and p53 (TP53) pathways. Loss of CASZ1 disrupts these controls, promoting proliferation, loss of adhesion, and invasion.
In HGC-27 cells, CASZ1 knockout amplifies the undifferentiated, metastatic phenotype by derepressing mesenchymal and pro-invasive genes. This model enhances proliferation, anchorage-independent growth, and EMT, marked by reduced E-cadherin and increased MMP expression. It enables dissection of molecular drivers of gastric cancer aggressiveness and screening for interventions that restore CASZ1 activity or its downstream tumor-suppressive pathways.
This knockout tool supports diverse applications in gastric cancer research. RT-qPCR and Western blot quantify changes in CASZ1 target expression; ChIP-qPCR assesses NuRD complex binding; and luciferase reporters map transcriptional regulation. Colony formation and transwell invasion assays evaluate clonogenicity and invasiveness. Drug response studies can probe altered chemosensitivity. For further details, contact Ascent Research.
