RRC ID 42112
著者 Miyoshi A, Kitajima Y, Sumi K, Sato K, Hagiwara A, Koga Y, Miyazaki K.
タイトル Snail and SIP1 increase cancer invasion by upregulating MMP family in hepatocellular carcinoma cells.
ジャーナル Br J Cancer
Abstract Loss of E-cadherin (E-cad) triggers invasion, metastasis, and dedifferentiation in various epithelial carcinomas. Recently, it has been reported that two transcription factors, Snail and SIP1 (Smad interacting protein 1), directly repress transcription of the E-cad gene by binding E-box on E-cad promoter. Our aim is to solve the molecular mechanism of Snail and SIP1 in hepatocellular carcinoma (HCC). We first showed an inverse correlation between E-cad and Snail/SIP 1 expression among five HCC lines with different phenotypes. The result indicated that undifferentiated, but not differentiated type expressed Snail/SIP1. Then, we established transfectants stably expressing Snail and SIP1 in two differentiated cells with E-cad expression. Suppressed expression of E-cad, morphologic change into fibroblastoid feature, and remarkable acceleration of invasion activity were observed in the transfectants. In reverse transcription-polymerase chain reaction series of genes relating to motility and invasion, we demonstrated striking evidence that matrix metalloproteinase (MMP-1), MMP-2, MMP-7, and MT1-MMP expressions were strongly upregulated by Snail. On the other hand, MMP-1, MMP-2, and MT1-MMP expressions were enhanced by SIP1 transfection, however, the intensity was weaker than that in Snail transfection. In conclusion, Snail or SIP1 expression may be induced during HCC progression, where Snail/SIP1 directly represses E-cad gene transcription and activates cancer invasion via the upregulation of the MMP gene family.
巻・号 90(6)
ページ 1265-73
公開日 2004-3-22
DOI 10.1038/sj.bjc.6601685
PII 6601685
PMID 15026811
PMC PMC2409652
MeSH Cadherins / biosynthesis Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology* DNA-Binding Proteins / pharmacology* Disease Progression Gene Expression Regulation, Neoplastic* Homeodomain Proteins / pharmacology* Humans Liver Neoplasms / genetics* Liver Neoplasms / pathology* Matrix Metalloproteinases / biosynthesis* Neoplasm Invasiveness / genetics* Repressor Proteins / pharmacology* Snail Family Transcription Factors Transcription Factors / pharmacology* Tumor Cells, Cultured Up-Regulation Zinc Finger E-box Binding Homeobox 2 Zinc Fingers
IF 5.791
引用数 207
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Hep G2 HuH-7(RCB1366)