The DMXL1 Knockout AGS Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line. This pool carries targeted disruption of the DMXL1 gene, which encodes a scaffold protein that bridges v-ATPase to the BLOC-1 complex, crucial for mTORC1 activation and lysosome-related organelle biogenesis. The polyclonal format provides a heterogeneous population, enabling robust loss-of-function studies while minimizing clonal artifacts, and is well-suited for investigating DMXL1-dependent processes in a physiologically relevant gastric epithelial background.
The AGS cell line is a standard model of human gastric adenocarcinoma with epithelial morphology, widely used to study gastric cancer proliferation, migration, and signaling. AGS cells retain key oncogenic pathways, including PI3K/AKT and mTOR, and serve as a platform for drug testing and functional genomics. Their adherent growth and transfectability make them amenable to CRISPR/Cas9 engineering, providing a relevant background for dissecting DMXL1 function in gastric cancer.
DMXL1 functions as a scaffold linking v-ATPase to the BLOC-1 complex, coordinating endosomal trafficking, lysosomal acidification, and mTORC1 activation. It interacts with v-ATPase subunits and LAMTOR1-5 components of the Ragulator, as well as AP-3 adaptors. Upstream, TFEB and MITF regulate DMXL1 expression in response to nutrient cues. DMXL1 loss disrupts v-ATPase-Ragulator coupling, impairing mTORC1 lysosomal recruitment and reducing phosphorylation of S6K and 4E-BP1. This alters autophagy flux, evidenced by LC3-II turnover changes, and compromises lysosomal function, underscoring DMXL1’s role in integrating growth signaling with catabolism.
In gastric adenocarcinoma, mTORC1 hyperactivation drives tumor growth. DMXL1 knockout in AGS cells enables dissection of mTORC1 regulation at the lysosomal surface, where v-ATPase and Ragulator converge. This model is suited to study endolysosomal trafficking defects, autophagy dependency, and stress responses. It also provides a system to explore lysosomotropic agent sensitivity and synthetic lethal interactions, bridging basic lysosome biology with translational gastric cancer research.
Researchers can use these cells for Western blotting of p-S6K and p-4E-BP1 to assess mTORC1, immunofluorescence for LAMP1/LAMP2, co-immunoprecipitation of v-ATPase subunits, and autophagy flux assays with LC3-II turnover. Cell viability and proliferation assays under nutrient deprivation or drug treatment reveal DMXL1-dependent vulnerabilities. These applications advance mTOR signaling, trafficking, and autophagy studies in gastric cancer. For further details, contact Ascent Research.
