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Acta Biochimica et Biophysica Sinica 2009 41(8):648-656; doi:10.1093/abbs/gmp053
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

TGF-β promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways

Hua Fu{dagger}, Zhongliang Hu{dagger}, Jifang Wen*, Kuansong Wang and Ying Liu

Department of Pathology, Basic School of Medicine, Central South University, Changsha 410013, China

* Correspondence address. Tel/Fax: +86-731-2650410; E-mail: jifangwen{at}hotmail.com


   Abstract

Transforming growth factor-β (TGF-β) 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-β, we applied the small interfering RNA (siRNA) technique to silence fascin1 in gastric cancer (GC) cells MKN45. Results showed that the effects of TGF-β1 on GC cells invasion and metastasis were mediated by tumor production of fascin1; furthermore, it was found that TGF-β1-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-β1-induced invasion and metastasis of GC cells, which involves JNK and ERK signaling pathways.

Keywords    gastric carcinoma; transforming growth factor-β1; Fascin1; RNA interference

Received: March 11, 2009; Accepted: April 15, 2009


{dagger} These authors contributed equally to this work.


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