PITX2 in pancreatic stellate cells promotes EMT in pancreatic cancer cells via the Wnt/β-catenin pathway  

作　　者：Di Wu Weibo Chen Yang Yang Yi Qin Guangchen Zu Yue Zhang Yong An Donglin Sun Xiaowu Xu Xuemin Chen 

机构地区：[1]Department of Hepatopancreatobiliary,Third Affiliated Hospital of Soochow University,Changzhou 213001,China [2]Department of Pancreatic Surgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第9期1393-1403,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81972250 and 81602054);the Young Talent Development Plan of Changzhou Health Commission(Nos.CZQM2021002 and CZQM2020005);the Young Talent Science and Technology Project of Changzhou Health Commission(No.QN202101);the Social Development Support Project of Changzhou Science and Technology Bureau(No.CE20225043);the Major Science and Technology Project of Changzhou Health Commission(Nos.ZD202006 and ZD202210).

摘　　要：Since the prognosis of patients with pancreatic cancer is very poor and there is a lack of treatment methods,this study is performed to investigate the function of PITX2 in pancreatic stellate cells(PSCs)in the progression of pancreatic cancer.Scientific hypotheses are proposed according to bioinformatics analysis and tissue microarray analysis.Stable knockdown of PITX2 in PSCs is achieved through lentiviral infection.The relative expressions of PITX2,α-SMA,vimentin,CTNNB1,AXIN1 and LEF1 are measured in wild-type PSCs and PITX2-knockdown PSCs.Proliferative capacity is measured by EdU assay.After coculture with PSCs,the proliferation,invasion and migration capacity of pancreatic cancer cells are tested.EMT and Wnt/β-catenin downstream genes of pancreatic cancer cells are investigated to reveal the potential mechanism.Bioinformatics analysis reveals that the PITX2 gene is highly expressed in stromal cells in pancreatic cancer and is correlated with squamous-type PDAC.Analysis of PDAC tissue microarray further demonstrates that high PITX2 level in stromal cells is correlated with poor prognosis in PDAC.After stable knockdown of PITX2 in PSCs,the relative protein levels ofα-SMA,vimentin,CTNNB1,AXIN1 and LEF1 are decreased,and the proliferative capacity of PSCs is also decreased.After coculture with PSCs,in which PITX2 expression is downregulated,the proliferation,invasion and migration capacities of pancreatic cancer cells are inhibited.Thus,our results show that PITX2-silenced PSCs inhibit the growth,migration and invasion of pancreatic cancer cells via reduced EMT and Wnt/β-catenin signaling.

关 键 词：pancreatic stellate cell PITX2 pancreatic cancer EMT Wnt/β-catenin pathway 

分 类 号：R73[医药卫生—肿瘤]