Silencing of ER-resident oxidoreductase PDIA3 inhibits malignant biological behaviors of multidrug-resistant gastric cancer  

作　　者：Danyang Song Meng Guo Kaichu Wu Jianyu Hao Yongzhan Nie Daiming Fan 

机构地区：[1]Department of Gastroenterology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China [2]State Key Laboratory of Cancer Biology,National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases,Air Force Military Medical University,Xi’an 710032,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第9期1216-1226,共11页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Sci-ence and Technology Support Project of National Clinical Medical Research Center for Digestive Diseases(No.2015BAI13B07);the National Natural Science Foundation of China(Nos.81430072 and 81702355);the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.81421003).

摘　　要：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.

关 键 词：PDIA3 GLYCOSYLATION multidrug resistance gastric cancer FN1 ITGA5 

分 类 号：R735.2[医药卫生—肿瘤]