TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways.
Transforming growth factor-beta (TGF-beta) is involved in actin cytoskeleton reorganization and tumor progression. Fascin1, an actin-binding protein, increases cell invasiveness and motility in various transformed cells. To determine whether fascin1 is an important mediator of the tumor response to TGF-beta, we applied the small interfering RNA (siRNA) technique to silence fascin1 in gastric cancer (GC) cells MKN45. Results showed that the effects of TGF-beta1 on GC cells invasion and metastasis were mediated by tumor production of fascin1; furthermore, it was found that TGF-beta1- induced fascin1 expression was suppressed by the specific inhibitors of JNK and ERK pathways, SP6001125 and PD98059, respectively, but not by transient transfection of Smad2 and Smad4 siRNA. Our data for the first time demonstrated that fascin1 is an important mediator of TGF-beta1-induced invasion and metastasis of GC cells, which involves JNK and ERK signaling pathways.
Fu
Hua
H
Department of Pathology, Basic School of Medicine, Central South University, Changsha, China.
Hu
Zhongliang
Z
Wen
Jifang
J
Wang
Kuansong
K
Liu
Ying
Y
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002352:Carrier Proteins; C502658:FSCN1 protein, human; D008840:Microfilament Proteins; D051899:Smad2 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases