RESUMEN
Glycosylation is a common posttranslational modification of proteins, which plays a role in the malignant transformation, growth, progression, chemoresistance, and immune response of tumors. Disulfide isomerase family A3 (PDIA3) specifically acts on newly synthesized glycoproteins to promote the correct folding of sugar chains. Studies have shown that PDIA3 participates in multidrug-resistant gastric cancer (MDR-GC). In this study, we performed western blot analysis and immunohistochemistry to identify PDIA3 expression. Cell proliferation was assessed by CCK-8 assay. Transwell assays were used to detect the migration and invasion abilities of cells. Immunoprecipitation coupled to mass spectrometry (IP-MS) analysis was employed to identify PDIA3-interacting proteins and the associated pathways in MDR-GC cells. Glycoprotein interactions and translocation were detected by immunofluorescence assay. The results showed that PDIA3 knockdown significantly inhibited the proliferation, invasion, and migration abilities of MDR-GC cells. Kyoto Encyclopedia of Genes and Genomes analysis of the IP-MS results showed that PDIA3 was closely associated with focal adhesion pathways in MDR-GC cells. Additionally, important components of focal adhesion pathways, including fibronectin-1 (FN1) and integrin α5 (ITGA5), were identified as pivotal PDIA3-binding glycoproteins. Knockdown of PDIA3 altered the cellular locations of FN1 and ITGA5, leading to abnormal accumulation. In conclusion, our results suggest that knockdown of PDIA3 inhibited the malignant behaviors of MDR-GC cells and influenced the translocation of FN1 and ITGA5.
Asunto(s)
Proliferación Celular , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Retículo Endoplásmico/enzimología , Silenciador del Gen , Proteínas de Neoplasias/biosíntesis , Proteína Disulfuro Isomerasas/biosíntesis , Neoplasias Gástricas/enzimología , Línea Celular Tumoral , Retículo Endoplásmico/genética , Retículo Endoplásmico/patología , Humanos , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteína Disulfuro Isomerasas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVES: Cavernous transformation of the portal vein (CTPV) is considered a sequel to extrahepatic portal vein obstruction. However, we have observed an unusual finding of cavernous vessels around a patent portal trunk in the liver hilum. The aim of our study is to describe the imaging features, clinical profiles, management, and outcome of these patients. MATERIAL AND METHODS: We re-evaluated the images of all consecutive non-malignant and non-cirrhotic patients with a diagnosis of CTPV admitted to our department between July 2002 and June 2010. The patients with a patent portal trunk were enrolled in this study. RESULTS: A total of five patients had cavernous vessels around a patent portal trunk. Of them, all presented with abdominal distension, and one with recurrent variceal bleeding. Hepatomegaly and splenomegaly were found in one and four patients, respectively. All but one with previous splenectomy had a decreased platelet count. Three patients had a high level of alkaline phosphatase and/or γ-glutamyl transferase. Serum bilirubin, albumin, and creatinine were in normal range. Endoscopy demonstrated varices in three patients. Mild ascites was detected in one patient by ultrasound. Conservative therapy was given to two patients with mild abdominal discomfort. Splenectomy or partial spleen embolization was given to two patients with hypersplenism. A transjugular intrahepatic portosystemic shunt insertion was performed in one patient for the prevention of recurrent variceal bleeding. All patients were alive during follow-up. CONCLUSIONS: These unusual findings led us to believe that cavernous vessels could develop around a patent portal trunk. Further studies are necessary to explore its pathogenesis.
