| 1 | Silencing of ER-resident oxidoreductase PDIA3 inhibits malignant biological behaviors of multidrug-resistant gastric cancer显示文摘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 integrinα5(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. | Danyang Song Meng Guo Kaichu Wu Jianyu Hao Yongzhan Nie Daiming Fan | 2021 | Acta Biochimica et Biophysica Sinica2021，53，9： | 2 |
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