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Loss of SLC26A9 Induces Gastric Carcinogenesis in Mice and Causes A More Aggressive Phenotype in Human Gastric Cancer
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Xuemei Liu1,
Dumin Yuan1,
Taolang Li1 |
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1Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University |
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| Background Previous study showed that Slc26a9 loss impairs parietal cell function and survival. We investigated whether Slc26a9 loss causes spontaneous gastric carcinogenesis in mice and plays a role in the development and progression in human gastric cancer (GC). Methods We investigated the role of Slc26a9 in the early stage of gastric cancer using the complete and gastric parietal cell-specific Slc26a9 deletion mice. Specifically, the influence of Slc26a9 deficiency on the development and progression of GC was analyzed on molecular, cellular and tissue levels.Results Complete as well as gastric parietal cell-specific Slc26a9 deletion in mice caused a spontaneous development of premalignant and malignant lesions in gastric epithelia, which was accompanied by the alteration of multiple markers for gastric stem cell differentiation, epithelial to mesenchymal transition (EMT), and mucosal barrier dysfunction in an inflammatory environment. Clinicopathological analysis of human gastric precancerous and cancerous tissues showed that SLC26A9 expression was progressively decreased from atrophic gastritis to GC and the downregulation of SLC26A9 correlated with patient’s short survival. SLC26A9 overexpression in AGS cells promoted apoptosis via inducing G2/M arrest, suppressed proliferation, migration and invasion as well as blocked EMT by inhibiting WNT signaling pathway. Conclusions Slc26a9 loss leads to spontaneous gastric carcinogenesis in mice and is involved in the progression of human GC. SLC26A9 might be a prognostic marker for GC. |
Index Term 1: Gastric Carcinogenesis
Index Term 2: Parietal Cell
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