Rab7 Is Associated with Poor Prognosis of Gastric Cancer and Promotes Proliferation, Invasion, and Migration of Gastric Cancer Cells
Autor: | Jianqing Lin, Qingzhi Yao, Zhong-Yi Zhang, Hui-Yong Liu, Jie Xu, Qiaonan Guo |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
G2 Phase
Male Cell 030204 cardiovascular system & hematology Flow cytometry S Phase 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Lab/In Vitro Research Stomach Neoplasms Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness Phosphorylation Promoter Regions Genetic Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Oncogene medicine.diagnostic_test Chemistry Reverse Transcriptase Polymerase Chain Reaction Arabinofuranosyluracil Carcinoma Cell Cycle rab7 GTP-Binding Proteins General Medicine Cell cycle Middle Aged Prognosis Up-Regulation medicine.anatomical_structure Cell culture rab GTP-Binding Proteins 030220 oncology & carcinogenesis Cancer cell Cancer research Female Lymph Nodes Proto-Oncogene Proteins c-akt |
Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
ISSN: | 1643-3750 1234-1010 |
Popis: | BACKGROUND Rab7 belongs to the Ras oncogene family. Many studies have shown that its dysfunction is associated with many types of malignant tumors, but its effect on the pathogenesis of gastric cancer (GC) is still unknown. Therefore, we investigated the effect and mechanism of Rab7 in GC. MATERIAL AND METHODS The expression of Rab7 in GC and adjacent tissues was detected by immunohistochemistry, Western blot analysis, and qRT-PCR. The relationship of Rab7 with clinicopathological parameters and prognosis was analyzed. The expressions of Rab7, PI3K, and AKT in GC cells were assessed by Western blot. Overexpressed and silenced GC cell lines were constructed and AGS cells were treated with LY294002. The proliferation capacity of GC cells was detected by CCK8 assay, cell cycle changes were detected by flow cytometry, and the invasion and migration abilities of GC cells were assessed by transwell assay. RESULTS The expression of Rab7 was upregulated in the samples and cells, and was positively correlated with lymph node metastasis but negatively correlated with histological differentiation and clinical prognosis. In cell function experiments, overexpression of Rab7 induced the transition from S phase to G2 phase and promoted the proliferation, invasion, and migration of GC cells. Our assessment of the molecular mechanism showed that Rab7 promoted the phosphorylation of PI3K and AKT in GC cells. Incubation with the PI3K inhibitor Ly294002 impaired the enhanced effect of Rab7 overexpression on proliferation, migration, and invasion abilities of GC cells. These results show that the Rab7 affects GC cell progression by modulating the PI3K/AKT pathway. CONCLUSIONS Rab7 could be a prognostic biomarker and therapeutic target of the PI3K/AKT pathway in GC. |
Databáze: | OpenAIRE |
Externí odkaz: |