MTA1 upregulation enhances stemness and chemoresistance of gastric cancer cells.

[OBJECTIVE] MTA1 (Metastasis-associated protein 1) is implicated in various malignancies, but its role in gastric cancer (GC) stemness and chemoresistance remains unclear. This study explores the effect of MTA1 on these processes and its underlying mechanisms.

[METHODS] MTA1 expression was assessed in GC tissues, paracancerous tissues, and cell lines. Lentiviral vectors were used to overexpress or silence MTA1 in AGS cells. Functional assays included MTT for drug sensitivity, flow cytometry for apoptosis, sphere formation to assess stemness, and Western blot for SOX-2, OCT-4, Bax, and Bcl2 expression. In addition, TCGA gastric cancer datasets were analyzed to evaluate the association of MTA1 expression with patient prognosis and predicted cisplatin sensitivity.

[RESULTS] MTA1 was significantly upregulated in GC tissues and cells. Its overexpression increased resistance to doxorubicin and cisplatin (↑IC50), inhibited apoptosis, and enhanced stemness via upregulation of SOX-2 and OCT-4. Conversely, MTA1 knockdown sensitized cells to chemotherapy, promoted apoptosis, and reduced stem-like properties. Public dataset analysis confirmed that MTA1 is upregulated in gastric cancer, associated with poor survival, and shows a trend toward reduced cisplatin sensitivity.

[CONCLUSION] MTA1 enhances chemoresistance and stemness in gastric cancer cells by modulating apoptosis and stemness-related proteins. It may serve as a novel therapeutic target for personalized GC treatment.