The ABCA13 Knockout MKN45 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from the human gastric adenocarcinoma cell line MKN45, harboring targeted gene disruption of ABCA13. This loss-of-function model enables detailed investigation of ABCA13’s tumor-suppressive roles in gastric cancer, particularly its regulation of Wnt/??-catenin signaling and lipid transport functions. The cell line provides researchers with a precise tool to dissect the molecular mechanisms by which ABCA13 deficiency contributes to oncogenic processes, including enhanced proliferation, invasion, and dysregulated signal transduction.
The host cell line MKN45 originates from a lymph node metastasis of a human gastric adenocarcinoma and is characterized as a poorly differentiated medullary type with a TP53 mutation. This genetic background recapitulates key features of aggressive gastric cancer, making MKN45 widely used in studies of gastric adenocarcinoma biology, signaling pathway alterations, and therapeutic response. The TP53 mutation adds a layer of genomic instability that synergizes with ABCA13 loss to model disease progression.
ABCA13 encodes an ATP-binding cassette transporter with putative lipid transport activity and functions as a tumor suppressor by inhibiting Wnt/??-catenin signaling. Mechanistically, ABCA13 interacts with low-density lipoprotein receptor-related protein 6 (LRP6) and Dishevelled-2 (DVL2) at lipid rafts, disrupting the assembly of the Wnt signalosome. Upstream, ABCA13 expression is frequently silenced via promoter hypermethylation mediated by DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Upon Wnt ligand (e.g., WNT3A) stimulation, lipid raft-dependent receptor complexes normally form; ABCA13 interferes with this process, preventing ??-catenin stabilization and nuclear translocation. Consequently, loss of ABCA13 unleashes TCF/LEF-mediated transcription of downstream targets such as MYC, CCND1, MMP7, and AXIN2, driving cell cycle progression and epithelial-mesenchymal transition markers like Vimentin and Snail.
In the MKN45 gastric adenocarcinoma context, ABCA13 knockout is expected to amplify Wnt/??-catenin signaling, directly enhancing tumorigenic properties including cell proliferation, colony formation, and invasiveness. This model thus allows systematic dissection of ABCA13’s role in restraining oncogenic signaling and provides a physiologically relevant system to study the interplay between genetic ablation and the TP53-mutated background in driving aggressive cancer phenotypes.
This cell line is suitable for a wide range of applications, including mechanistic studies of Wnt/??-catenin pathway regulation, investigation of tumor suppressor function, epigenetic regulation of ABC transporter genes, and drug screening for Wnt pathway inhibitors or epigenetic modulators. Researchers can employ representative assays such as Western blotting for pathway components, RT-qPCR for target gene expression, dual-luciferase TOP/FOP reporter assays for ??-catenin activity, cell proliferation and colony formation assays, Transwell invasion assays, co-immunoprecipitation to probe ABCA13 interactions with LRP6 and DVL2, and cholesterol efflux assays to assess lipid transporter function. For more information, please contact Ascent Research.
