- AGS cells, a widely used human gastric adenocarcinoma cell line, do not express functional E-cadherin due to epigenetic silencing of the CDH1 gene, which encodes this critical adhesion molecule.
- The primary mechanism underlying this loss is promoter hypermethylation, a common epigenetic modification that suppresses gene transcription. As a result, E-cadherin mRNA and protein levels are extremely low or absent in AGS cells. This loss is not due to a genetic mutation or deletion, but rather a reversible change—studies have shown that treating AGS cells with DNA-demethylating agents such as 5-aza-2′-deoxycytidine can partially restore E-cadherin expression, confirming the epigenetic nature of the silencing.
- The lack of E-cadherin has significant consequences for AGS cell behavior. E-cadherin is a key component of adherens junctions and plays a fundamental role in maintaining epithelial cell-cell adhesion, polarity, and tissue architecture.
- Without E-cadherin, AGS cells exhibit a non-polarized, loosely adherent phenotype, which mimics certain features of invasive and poorly differentiated gastric cancers, particularly the diffuse type. This makes AGS cells a relevant model for studying the processes underlying epithelial–mesenchymal transition (EMT), tumor progression, and invasive behavior.
- In research on Helicobacter pylori, the absence of E-cadherin in AGS cells offers both advantages and limitations. On one hand, it makes these cells less suitable for studying the direct disruption of adherens junctions—such as the destabilization of the E-cadherin/β-catenin complex—by H. pylori CagA. On the other hand, the lack of junctional sequestration allows for more pronounced β-catenin signaling responses, as β-catenin is not held at the membrane and is more readily available to translocate to the nucleus. This characteristic has been particularly valuable in studies examining CagA-dependent activation of Wnt/β-catenin signaling pathways, oncogenic transformation, and cellular proliferation.
- Overall, the absence of E-cadherin in AGS cells provides a unique environment for dissecting junction-independent effects of CagA, and has contributed significantly to our understanding of how H. pylori manipulates host signaling and promotes gastric carcinogenesis.
