β-Catenin Regulates the Expression of the Matrix Metalloproteinase-7 in Human Colorectal Cancer

Brabletz, Thomas; Jung, Andreas; Dağ, Serpil; Hlubek, Falk; Kirchner, Thomas

doi:10.1016/s0002-9440(10)65204-2

Cited by 610 publications

(488 citation statements)

References 26 publications

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“…(Brabletz et al, 1998). Although we found a significant correlation between nuclear beta-catenin expression and ulcerative growth and also observed that most of the ulcerative tumours were rectal carcinomas (Table 1), we did not observe a significant relationship between tumour localisation and nuclear (He et al, 1998), cyclin D1 (Tetsu and McCormick, 1999), gastrin (Koh et al, 2000), PPARS (He et al, 1999) MMP-7 (Brabletz et al, 1999;Crawford et al, 1999) are warranted. Some factors such as c-myc, cyclin D and gastrin reportedly relate to tumour proliferation, while others are related to tumour invasion.…”

Section: Discussionmentioning

confidence: 47%

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Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

et al. 2002

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Although most colorectal cancer develops based on the adenoma -adenocarcinoma sequence, morphologically, colorectal cancer is not a homogeneous disease entity. Generally, there are two distinct morphological types: polypoid and ulcerative colorectal tumours. Previous studies have demonstrated that K-ras codon 12 mutations are preferentially associated with polypoid growth of colorectal cancer; however, little is known about the molecular mechanism that determines ulcerative growth of colorectal cancer. b-catenin complex plays a critical role both in tumorigenesis and morphogenesis. We examined the differential expression of b-catenin and its related factors among different types of colorectal cancer in order to determine any relationship with gross tumour morphology. Immunohistochemical staining of b-catenin, E-cadherin and MMP-7 was performed on 51 tumours, including 26 polypoid tumours and 25 ulcerative tumours. Protein truncation tests and single-strand conformational polymorphism for mutation of the adenomatous polyposis coli tumour suppressor gene, as well as singlestrand conformational polymorphism for the mutation of b-catenin exon 3 were also done. Nuclear expression of b-catenin was observed in 18 out of 25 (72%) cases of ulcerative colorectal cancer and seven out of 26 (26.9%) cases of polypoid colorectal cancer. A significant relationship of nuclear b-catenin expression with ulcerative colorectal cancer was found (P50.001). However, this finding was independent of adenomatous polyposis coli tumour suppressor gene mutation and Ecadherin expression. Together with previous data, we propose that different combinations of genetic alterations may underlie different morphological types of colorectal cancer. These findings should be taken into consideration whenever developing a new genetic diagnosis or therapy for colorectal cancer.

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Section: Discussionmentioning

confidence: 47%

“…Some factors such as c-myc, cyclin D and gastrin reportedly relate to tumour proliferation, while others are related to tumour invasion. MMP-7 is regulated by b-catenin expression (Brabletz et al, 1999) and is a proteolytic enzyme related to tumour invasion. It may well be reasonable to relate proteolysis to ulcerative growth.…”

Section: Discussionmentioning

confidence: 99%

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

et al. 2002

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“…LEF1 (Hovanes et al, 2001), MMP7 (Brabletz et al, 1999), cyclin D1 (Tetsu and McCormick, 1999) and CD44 (Wielenga et al, 1999) are all reported to be direct or indirect targets of b-catenin-TCF/LEF, confirming that Wnt signaling is blocked by SFRP2 in SNU638 cells (Table 2). We also found that significant numbers of genes related to cellular proliferation, growth or apoptosis are repressed or induced by SFRP2.…”

Section: Changes In Gene Expression Profiles Induced By Overexpressiomentioning

confidence: 68%

Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer

et al. 2007

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Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (b-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in GC. We frequently observed nuclear b-catenin accumulation (13/15; 87%) and detected the active form of b-catenin in most (12/16; 75%) GC cell lines. CpG methylation-dependent silencing of SFRP1, SFRP2 and SFRP5 was frequently seen among GC cell lines (SFRP1, 16/16, 100%; SFRP2, 16/ 16, 100%; SFRP5, 13/16, 81%) and primary GC specimens (SFRP1, 42/46, 91%; SFRP2, 44/46, 96%; SFRP5, 30/46, 65%), and treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine rapidly restored SFRP expression. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor transcriptional activity, suppressed cell growth and induced apoptosis in GC cells. Analysis of global expression revealed that overexpression of SFRP2 repressed Wnt target genes and induced changes in the expression of numerous genes related to proliferation, growth and apoptosis in GC cells. It thus appears that aberrant SFRP methylation is one of the major mechanisms by which Wnt signaling is activated in GC.

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“…), some of them having important implications in cancer progression. [27][28][29][30][31][32][33][34][35][36] These independent data from the literature therefore suggest that a reorganisation of E-cadherin/b-catenin and an overexpression of MCP-1 in tumour cells are 2 events associated with cancer progression. This prompted us to investigate the potential regulation of MCP-1 by the b-catenin/TCF pathway.…”

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confidence: 99%

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

Mestdagt

Polette

Butticè

et al. 2005

Intl Journal of Cancer

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The loss of E-cadherin expression and the translocation of b-catenin to the nucleus are frequently associated with the metastatic conversion of epithelial cells. In the nucleus, b-catenin binds to the TCF/LEF-1 (T-cell factor/ lymphoid enhancer factor) transcription factor family resulting in the activation of several genes, some of them having important implications in tumour progression. In our study, we investigated the potential regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) expression by the b-catenin/TCF pathway. This CC-chemokine has been implicated in tumour progression events such as angiogenesis or tumour associated macrophage (TAM) infiltration. We thus demonstrated that MCP-1 expression correlates with the reorganization of the E-cadherin/b-catenin complexes. Indeed, MCP-1 was expressed by invasive breast cancer cells (MDA-MB-231, BT549 and Hs578T), which do not express E-cadherin but was not produced by noninvasive breast cancer cell lines (MCF7 and T47D) expressing high level of E-cadherin. In addition, the MCP-1 promoter was activated in BT549 breast cancer cells transfected with b-catenin and TCF-4 cDNAs. The MCP-1 mRNA level was similarly upregulated. Moreover, we showed that MCP-1 mRNA was downregulated after transfection with a siRNA against b-catenin in both BT549 and Hs578T cells. Our results therefore identify MCP-1 as a target of the b-catenin/TCF/LEF pathway in breast tumour cells, a regulation which could play a key role in breast tumour progression. ' 2005 Wiley-Liss, Inc.Key words: MCP-1; b-catenin; breast cancer Chemokines constitute a superfamily of proinflammatory cytokines that are implicated in tumour progression, modulating not only host tumour-specific immunological response but also angiogenesis or tumour cell invasion and proliferation. 1-3 Monocyte chemotactic protein-1 (MCP-1) or CCL2 is a CC-chemokine that specifically attracts monocytes and memory T cells. It has been particularly implicated in processes characterized by mononuclear cell infiltration including breast cancer. 4,5 In some models, MCP-1 has been shown to display an antitumoral effect. 6,7 Nevertheless, a large number of studies demonstrate that MCP-1 facilitates tumour progression through its ability to recruit stromal cells including tumour associated macrophages (TAMs) and endothelial cells. 7-10 A pro-angiogenic role of MCP-1 has been demonstrated in many systems, facilitating tumour growth and dissemination. 8,9,11,12 Moreover, a direct effect of MCP-1 on tumour cell migration in vitro has also been described. 13 Recently, Lebrecht et al. 14 have correlated an increased MCP-1 serum level with an advanced breast tumour stage and the presence of lymph node metastasis. In the same way, Amann et al. 15 reported a significant association between MCP-1 urinary levels and tumour stage and grade. They suggested a use of its urinary level as prognosis marker in bladder cancer. The correlation between MCP-1 expression and a poor prognosis was also demonstrated for the squamous cell carcinoma of the oeso...

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β-Catenin Regulates the Expression of the Matrix Metalloproteinase-7 in Human Colorectal Cancer

Cited by 610 publications

References 26 publications

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Nuclear β-catenin expression is closely related to ulcerative growth of colorectal carcinoma

Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer

Transactivation of MCP‐1/CCL2 by β‐catenin/TCF‐4 in human breast cancer cells

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