英语翻译Tissue transglutaminase inhibits autophagy in pancreatic cancer cells.Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes.However,the rol

英语翻译Tissue transglutaminase inhibits autophagy in pancreatic cancer cells.Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes.However,the rol
英语翻译
Tissue transglutaminase inhibits autophagy in pancreatic cancer cells.
Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes.However,the role and the mechanisms that regulate TG2 expression remain elusive.Here,we provide evidence that protein kinase Cdelta (PKCdelta) regulates TG2 expression,which in turn inhibits autophagy,a type II programmed cell death,in pancreatic cancer cells that are frequently insensitive to standard chemotherapeutic agents.Rottlerin,a PKCdelta-specific inhibitor,and PKCdelta small interfering RNA (siRNA) down-regulated the expression of TG2 mRNA and protein and induced growth inhibition without inducing apoptosis in pancreatic cancer cells.Inhibition of PKCdelta by rottlerin or knockdown of TG2 protein by a TG2-specific siRNA resulted in a marked increase in autophagy shown by presence of autophagic vacuoles in the cytoplasm,formation of the acidic vesicular organelles,membrane association of microtubule-associated protein 1 light chain 3 (LC3) with autophagosomes,and a marked induction of LC3-II protein,important hallmarks of autophagy,and by electron microscopy.Furthermore,inhibition of TG2 by rottlerin or by the siRNA led to accumulation of green fluorescent protein (GFP)-LC3-II in autophagosomes in pancreatic cancer cells transfected with GFP-LC3 (GFP-ATG8) expression vector.Knockdown of Beclin-1,a specific autophagy-promoting protein and the product of Becn1 (ATG6),inhibited rottlerin-induced and TG2 siRNA-induced autophagy,indicating that Beclin-1 is required for this process.These results revealed that PKCdelta plays a critical role in the expression of TG2,which in turn regulates autophagy.In conclusion,these results suggest a novel mechanism of regulation of TG2 and TG2-mediated autophagy in pancreatic cancer cells.

英语翻译Tissue transglutaminase inhibits autophagy in pancreatic cancer cells.Elevated expression of tissue transglutaminase (TG2) in cancer cells has been implicated in the development of drug resistance and metastatic phenotypes.However,the rol
组织转抑制吞噬的胰腺癌细胞.
高架表达组织转（ TG2 ）在肿瘤细胞中有牵连的发展和转移耐药表型.然而,作用和机制,规范TG2表达仍然难以实现.在这里,我们提供的证据表明,蛋白激酶Cdelta （ PKCdelta ）规定TG2表达,进而抑制吞噬,一个第二类程序性细胞死亡,在胰腺癌细胞,这些标准往往不敏感,化疗药物.Rottlerin ,一个PKCdelta特定的抑制剂,并PKCdelta小干扰RNA （ RNA干扰）下调表达TG2 mRNA和蛋白的诱导生长抑制和诱导细胞凋亡与胰腺癌细胞.抑制PKCdelta的rottlerin或击倒的TG2蛋白质的TG2特定的siRNA导致显着增加,表明自噬存在自泡在细胞质,形成酸性囊泡细胞,膜协会微管相关蛋白1轻链3 （ LC3 ）与autophagosomes ,并显着诱导LC3 - Ⅱ蛋白的重要标志吞噬,并通过电子显微镜.此外,抑制TG2的rottlerin或小分子干扰核糖核酸导致积累的绿色荧光蛋白（ GFP ） - LC3 - II在autophagosomes在胰腺癌细胞转染绿色荧光蛋白LC3 （绿色荧光蛋白ATG8 ）表达载体.击倒的Beclin - 1 ,一个具体吞噬促进蛋白质和产品的Becn1 （ ATG6 ） ,抑制rottlerin诱导和TG2的siRNA诱导的自噬,表明Beclin - 1需要为这一进程.这些结果表明,PKCdelta方面起着关键作用的表达TG2 ,这反过来又规定吞噬.总之,这些结果表明了一种新机制的调节TG2和TG2介导自噬在胰腺癌细胞.