RESUMEN
BACKGROUND: Gastric cancer (GC) is the fourth most commonly found cancer and the second- highest cause of cancer-related death worldwide. TROP2 overexpression is closely related to many cancers, including gastrointestinal tumors. DSG2 is an important protein in cell adhesion, and its loss affects cell migration. AIMS AND OBJECTIVE: This study aimed to explore the specific mechanism of TROP2 in promoting gastric cancer and provide a basis for the prevention and treatment of gastric cancer. METHOD: DSG2 was identified as an interacting protein of TROP2 in GC cells by coimmunoprecipitation and mass spectrometry. The regulated behavior of TROP2 on DSG2 expression was investigated with TROP2 over-expressure or knockdown. Cell-cell adhesion capacity mediated by DSG2 was evaluated by adhesion-related assays. Electron microscope observation was made for accessing GC tumor desmosome assembly. Proteins in EGFR/AKT and DSG2/PG/ß-catenin pathways were evaluated by western blotting. RESULT: This study suggests that abundant expression of TROP2 in GC cells lessened DSG2 levels as well as desmosome adhesion, increased cell invasion and migration, and promoted malignant progression through EGFR/AKT and DSG2/PG/ß-catenin pathways. CONCLUSION: TROP2 promotes cell invasion and migration in gastric cancer by decreasing DSG2 expression through EGFR/AKT and DSG2/PG/ß-catenin pathways.
Asunto(s)
Antígenos de Neoplasias , Moléculas de Adhesión Celular , Desmogleína 2 , Neoplasias Gástricas , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Desmogleína 2/genética , Desmogleína 2/metabolismo , Receptores ErbB/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , beta Catenina/metabolismoRESUMEN
To solve issues of low consolidation strength, poor dust suppression effect, and secondary pollution of the current coal dust suppressors, a greener and higher-consolidation-strength composite dust suppressor was synthesized by the radical polymerization of xanthan gum (XG) as the graft substrate, methyl acrylate (MA), and vinyl acetate (VAc) as the graft monomers. Taking compressive strength as the main optimization index and viscosity and surface tension as the secondary indices, the optimum ratio of MA:VAc was 3:5 and the optimum solid content was 2%. Experiments reveal that the prepared dust suppressant can naturally infiltrate into coal to form a hard solidified layer. At a wind speed of 10 m/s, the solidified layer still maintained structural integrity, indicating that the dust suppressant exhibits a good dust fixation effect. The dust suppressant can not only maintain relatively stable performance for a period of time but also degrade naturally. Furthermore, molecular dynamics simulation reveals not only the interaction mechanism between coal molecules and the dust suppressor but also the wetting mechanism of the dust suppressor. Experimental and simulation results reveal that as a multifunctional dust suppressor with excellent performance, the as-prepared dust suppressor demonstrates the immense potential for the control of coal dust. Graphical abstract.