Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas

Harada, Tadao; Arii, Shigeki; Mise, Masahiro; Imamura, Takashi; Higashitsuji, Hiroaki; Furutani, Masaharu; Niwano, Mototaka; Ishigami, Shunichi; Fukumoto, Manabu; Seiki, Motoharu; Sato, Hiroshi; Imamura, Masayuki

doi:10.1016/0168-8278(88)80010-2

Cited by 63 publications

(27 citation statements)

References 29 publications

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“…Harada et al and Arii et al have demonstrated that MT1-MMP is involved in hepatocarcinoma cell migration (29,30); however, the molecular mechanism is unknown. In searching for the underlying mechanism of α1-PDX inhibition of the migration and invasion of MG-63 and Saos-2 osteosarcoma cells in the present study, the expression levels of MT1-MMP mRNA and protein in MG-63 and Saos-2 osteosarcoma cells upon α1-PDX treatment were detected.…”

Section: Discussionmentioning

confidence: 99%

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

Liu

Wang

et al. 2014

Oncology Letters

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This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1-antitrypsin Portland (α1-PDX). Wound-healing and Transwell assays were used for the detection of the effects of α1-PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription-polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1-MMP), Wnt and β-catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1-MMP gene transcription activity. The results showed that α1-PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1-MMP decreased evidently upon α1-PDX treatment, paralleled with reductions in the expression levels of Wnt and β-catenin. Further analysis of the transcriptional activity of MT1-MMP revealed that the α1-PDX-induced downregulation of the levels of MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that α1-PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

Liu

Wang

et al. 2014

Oncology Letters

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“…Overexpression of MT1 -MMP has enhanced pulmonary metastasis in animal models (Tsunezuka et al, 1996) and the invasiveness of MDCK cells in other experiments (Hotary et al, 2000). Expression of MT1 -MMP is associated with invasion and/or metastasis of human cancers (Harada et al, 1998;Kikuchi et al, 2001;Mimori et al, 2001;Shimada et al, 2000), and it also plays a role in cell motility mediated by CD44-shedding (Kajita et al, 2001). It is noteworthy that Claudin-1, Laminin-5 g2 and CD44 are also up-regulated by the b-catenin/Tcf4 complex Hlubek et al, 2001;Wielenga et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers

et al. 2002

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Genetic alterations of APC and CTNNB1 (b-catenin) have been identified in a number of human cancers including tumors arising in the colon and liver. Mutations in these genes lead to abnormal accumulation of b-catenin and constitutive activation of target genes in the Wnt signaling pathway. To clarify the precise role of accumulated bcatenin in colorectal carcinogenesis, we searched for genes involved in the b-catenin/Tcf signaling pathway by cDNA microarray. MT1 -MMP (membrane-type matrix metalloproteinase) was among 84 genes that were downregulated after b-catenin had been depleted by transduction of wild-type APC in SW480 cells. Expression of MT1 -MMP was elevated in 22 of 24 colon carcinomas we examined. Reporter assays and an electromobility-shift assay revealed a DNA fragment between 71169 bp and 71163 bp in the 5' flanking region of this gene to be a target of the b-catenin/Tcf4 complex. Our results indicate that MT1 -MMP is a direct down-stream target in the Wnt signaling pathway, and that one of the ways accumulated b-catenin contributes to colorectal carcinogenesis is by transactivating this gene.

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“…Alterations of the TPs described herein are detected in solid and hematologic tumors (Table 1) (Ueno et al, 1997;Afzal et al, 1998;Harada et al, 1998;Kitagawa et al, 1998;Curran and Murray, 1999;Ellerbrock and Stack, 1999;Ishigaki et al, 1999;Brinckerhoff et al, 2000;Ellenrieder et al, 2000;Neal et al, 2000;Antczak et al, 2001a, b;Fillmore et al, 2001;Kerkela et al, 2001;Soderstrom et al, 2001;Hashida et al, 2002;Mishima et al, 2002;Seiki and Yana, 2003). In some cases, malignancy is associated with a marked increase in TP expression, whereas in others it is associated with downregulation.…”

Section: Cancermentioning

confidence: 99%

Transmembrane proteases in cell growth and invasion: new contributors to angiogenesis?

2004

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Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas

Cited by 63 publications

References 29 publications

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers

Transmembrane proteases in cell growth and invasion: new contributors to angiogenesis?

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