Dataset Information

DKK1 Promotes Epithelial-Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway.

ABSTRACT: Chemotherapy is a classical method of cancer treatment. Cisplatin-based chemotherapy is a traditional and essential therapeutic approach in gastric cancer treatment. However, the development of drug resistance during treatment is a major obstacle that limits their further application, and molecular changes have occurred in the development of drug resistance. Here, we found that Dickkopf-related protein 1 (DKK1) is highly expressed in gastric cancer and related to poor prognosis in gastric cancer patients through public database mining. Next, we also identified that DKK1 is highly expressed in CDDP-resistant gastric cancer cell lines, supporting the notion that DKK1 is a necessary regulator of CDDP resistance. In terms of mechanistic research, our data reveal that DKK1 was able to activate the PI3K/AKT pathway and affect epithelial-to-mesenchymal transition, further contributing to CDDP resistance. Genetic knockdown and pharmacological inhibition of DKK1 recovered CDDP sensitivity both in vitro and in vivo. Therefore, our study highlights the potential of targeted inhibition of DKK1 to reverse CDDP resistance and alleviate metastatic properties in gastric cancer.

SUBMITTER: Li J

PROVIDER: S-EPMC10571993 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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DKK1 Promotes Epithelial-Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway.

Li Jian J Zhang Yaqiong Y Ye Fangzhou F Qian Peiyu P Qin Zhe Z Li Deming D Ye Li L Feng Li L

Cancers 20230927 19

Chemotherapy is a classical method of cancer treatment. Cisplatin-based chemotherapy is a traditional and essential therapeutic approach in gastric cancer treatment. However, the development of drug resistance during treatment is a major obstacle that limits their further application, and molecular changes have occurred in the development of drug resistance. Here, we found that Dickkopf-related protein 1 (DKK1) is highly expressed in gastric cancer and related to poor prognosis in gastric cancer ...[more]

PMID: 37835450

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Project description:Background: Spinal cord glioma (SCG), a rare subset of central nervous system (CNS) glioma, represents a complex challenge in neuro-oncology. There has been research showing that Retinol Dehydrogenase 10 (RDH10) may be a tumor promoting factor in brain glioma, but the biological effects of RDH10 remain undefined in SCG. Methods: We performed gene set enrichment analysis (GSEA) and unsupervised clustering analysis to investigate the roles of EMT (epithelial-mesenchymal transition) in glioma. DEG (differently expressed gene) screening and correlation analysis were conducted to filter the candidate genes which were closely associated with EMT process in SCG. Enrichment analysis and GSVA (Gene Set Variation Analysis) were conducted to investigate the potential mechanism of RDH10 for SCG. Trans-well and healing assay were performed to explore the role of RDH10 in the invasion of SCG. Western blotting was performed to evaluate the levels of markers in PI3K-AKT and EMT pathway. In vivo tests were conducted to verify the role of RDH10 in EMT process. Results: Bioinformatic analysis demonstrated the EMT pathway was associated with dismal prognosis of glioma. Further analysis demonstrated that RDH10 showed the strongest correlation with the EMT process. Retinol Dehydrogenase 10 expression was significantly increased in SCG tissues, correlating with advanced tumor grade and unfavorable prognosis. Functional analysis indicated that decreasing RDH10 levels impeded the invasive and migratory abilities of SCG cells, whereas increasing RDH10 levels augmented them. Enrichment analysis and western blot revealed that RDH10 regulated EMT process of SCG by PI3K-AKT pathway. We observed that the enhanced invasion ability and increased EMT-related protein induced by RDH10 overexpression can be suppressed by PI3K-AKT pathway inhibitor (LY294002). Conclusion: Our research found that RDH10 was an effective biomarker associated with tumor grade and prognosis of SCG. RDH10 could regulate EMT process of SCG through PI3K-AKT pathway.

Dataset Information

DKK1 Promotes Epithelial-Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway.

Publications

DKK1 Promotes Epithelial-Mesenchymal Transition and Cisplatin Resistance in Gastric Cancer via Activation of the PI3K/AKT Pathway.

Similar Datasets

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