Epigenetic versus genetic alterations in the inactivation of E-cadherin

Strathdee, Gordon

doi:10.1016/s1044-579x(02)00057-3

Cited by 170 publications

(118 citation statements)

References 55 publications

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“…24 Aberrant expression of H-cadherin and E-cadherin caused by CDH13 and CDH1 promoter hypermethylation has been reported in a variety of tumors and their effect on tumorigenesis and invasiveness has been elucidated. 3,4,11 In the current study, decreased mRNA expression of CDH13 was detected in 54% (28/52) of pituitary tumor samples; E-cadherin protein expression was lost in 21 (30%) tumors and significantly reduced in 22 (32%) tumors. In addition, tumorspecific hypermethylation of CDH13 and CDH1 was detected in 30 and 36% of pituitary adenomas including all major types and in all tumor stages, respectively.…”

Section: Discussionsupporting

confidence: 49%

“…2 Mutation of the CDH1 gene can lead to the expression of a non-functional protein. 11 The binding of the transcription factor Snail and/or Slug to E2 boxes in the CDH1 promoter results in gene silencing. 37 Dysadherin interferes with E-cadherin function by downregulation of protein levels without affecting mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

“…Decrease or loss of Ecadherin expression accompanied by CDH1 promoter methylation has been reported in many human cancers. 11 In pituitary adenomas, E-cadherin expression might play a variety of roles in different tumor subtypes. Our previous studies showed that the decreased expression of E-cadherin was related to aggressive behavior of prolactinomas and was associated with the formation of fibrous bodies in GH cell adenomas.…”

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confidence: 99%

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Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

et al. 2007

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The gene products of CDH13 and CDH1, H-cadherin and E-cadherin, respectively, play a key role in cell-cell adhesion. Inactivation of the cadherin-mediated cell adhesion system caused by aberrant methylation is a common finding in human cancers, indicating that the CDH13 and CDH1 function as tumor suppressor and invasion suppressor genes. In this study, we analyzed the expression of H-cadherin mRNA and E-cadherin protein in 5 normal pituitary tissues and 69 primary pituitary adenomas including all major types by quantitative real-time RT-PCR (qRT-PCR) and immunohistochemistry, respectively. Reduced expression of H-cadherin was detected in 54% (28/52) of pituitary tumors and was significantly associated with tumor aggressiveness (Po0.05). E-cadherin expression was lost in 30% (21 of 69) and significantly reduced in 32% (22 of 69) of tumors. E-cadherin expression was significantly lower in grade II, III, and IV than in grade I adenomas (P ¼ 0.015, P ¼ 0.029, and P ¼ 0.01, respectively). Using methylation-specific PCR (MSP), promoter hypermethylation of CDH13 and CDH1 was detected in 30 and 36% of 69 adenomas, respectively, but not in 5 normal pituitary tissues. Methylation of CDH13 was observed more frequently in invasive adenomas (42%) than in non-invasive adenomas (19%) (Po0.05) and methylation of CDH1 was more frequent in grade IV adenomas compared with grade I adenomas (Po0.05). Methylation of either CDH13 or CDH1 was identified in 35 cases (51%) and was more frequent in grade IV invasive adenomas than in grade I non-invasive adenomas (Po0.05 and Po0.05, respectively). Downregulation of expression was correlated with promoter hypermethylation in CDH13 and CDH1. In conclusion, the tumor-specific downregulation of expression and methylation of CDH13 and CDH1, alone or in combination, may be involved in the development and invasive growth of pituitary adenomas.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

et al. 2007

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“…It is rapidly phosphorylated by glycogen synthase kinase 3b (GSK3b) and subsequently ubiquitylated and degraded by the proteasome pathway [20]. As a result of transcriptional repression, the E-cadherin promoter is frequently found hypermethylated in a large subset of cancer cases [21]. E-cadherin can also be downregulated at the protein level.…”

Section: Changes In Cell-cell and Cell-matrix Adhesionmentioning

confidence: 99%

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Kopfstein

Christofori

2006

Cell. Mol. Life Sci.

209

160

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Abstract. The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix Cell. Mol. Life Sci. 63 (2006) 449-468 1420-682X/06/040449-20 DOI 10.1007/s00018-005-5296-8 © Birkhäuser Verlag, Basel, 2006 adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic process.

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“…Transcription of E-cadherin is directly regulated by methylation and repression of promoter activity. During carcinogenesis, methylation of the E-cadherin promoter is associated with reduced E-cadherin expression, disease progression, and metastasis (6). Transcription of E-cadherin is also regulated by zinc finger proteins of the Slug/Snail family and Smad-Interacting Protein (7,8).…”

Section: Introductionmentioning

confidence: 99%

Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin

Zhou

Yan

et al. 2009

Molecular Cancer Therapeutics

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Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of cell-cell adhesion and an increased cell invasion. Many studies have shown the antiproliferative activities of luteolin on cancer cells. However, the effects of luteolin on invasion of cancer cells remain unclear. In this article, we show that luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. We found that Luteolin induced expression of E-cadherin through mdm2. Overexpression of mdm2 or knockdown of E-cadherin could restore invasion of PC3 cells after luteolin treatment. Luteolin inhibits mdm2 through AKT and overexpression of active AKT attenuated luteolin-induced expression of E-cadherin, suggesting that luteolin regulates E-cadherin through AKT/mdm2 pathway. The in vivo experiments showed that luteolin inhibited spontaneous lung metastasis of PC3 cells implanted onto the nude mice. These findings provide a new sight into the mechanisms that luteolin is against cancer cells, and suggest that molecular targeting of E-cadherin by luteolin may be a useful strategy for treatment of invasive prostate cancers.

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Epigenetic versus genetic alterations in the inactivation of E-cadherin

Cited by 170 publications

References 55 publications

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin

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