Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移.pdfVIP

Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移--第1页

Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移

石萌;南兴建;李文静;王亚东;郑浩轩

【摘要】ObjectiveToexplorethepossiblemechanismsofthemetastasis

promotioninducedbyFassignalingpathwayingastriccancer.Methods

GastriccancercelllineAGSwastreatedwithlow-doseFasLandthe

alterationofEMT(epithelial-mesenehymaltransition)biologymarkers

weredetectedbyimmunoblotandenzymelinkedimmunosorbent

assay,respectively.TwotranscriptionfactorsSnailandTwistwerestablely

knocked-down,andtranswellchambermigrationassaywasperformedto

measurethemotilityofthepretreatedgastriccancercells.Immunoblot

wasusedtoassesstheactivationsandthemotilitychangesofAGSafter

pre-treatedwithinhibitorofrelativepathwaysduringtheprocedure.

ResultsFasLinducedtheoccurrenceofEMTinAGScellline,whichmight

contributetothemotilityandmetastasisofgastriccancercells.Inthe

processofEMT,ERK1/2signalingpathwaywasactivatedandthe

suppressionofthispathwayinhibitedtheFasinducedEMTandimproved

themigrationabilityofgastriccancercells.Theexpressionvariationof

relevantbiologymarkersingastriccancertissueswascorrespondtoEMT

occurrence.ConclusionFassignalingpathwaycanpromotethemetastasis

ofAGScelllinethroughEMTwiththeactivationofERK1/2pathway.%目的：

探讨Fas信号通路促进胃癌细胞侵袭转移的可能相关机制。方法以低浓度FasL处

理胃癌细胞株AGS，免疫印迹及ELISA检测上皮间质转化（epithelial-

mesenehymaltransition,EMT）的分子生物学标记改变；稳定沉默Snail及

Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移--第1页

Fas信号通路通过诱导EMT促进胃癌细胞的侵袭转移--第2页

Twist转录因子，transwell小室侵袭实验检测FasL处理后胃癌细胞的侵袭能力；

免疫印迹检测信号通路激活状态及相应的抑制效应。结果FasL可以诱导AGS细

胞株出现EMT表型，并可促进胃癌细胞的侵袭转移能力。同时该过程中出现

ERK1/2信号通路的激活，而抑制ERK1/2信号通路，可以抑制FasL诱导EMT及

提高肿瘤侵袭能力的作用。