Characteristics of Smooth Muscle Cell Lipoprotein Binding Proteins (p105/p130) as T-Cadherin and Regulation by Positive and Negative Growth Regulators

Kuzmenko, Yelena S.; Stambolsky, Dmitry; Kern, Frances; Bochkov, Valery N.; Tkachuk, Vsevolod A.; Resink, Thérèse J.

doi:10.1006/bbrc.1998.8645

Cited by 25 publications

(25 citation statements)

References 35 publications

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“…In addition to its specific expression in certain regions of the brain, T-cad is expressed in skeletal muscle, heart, kidney and aortic tissues (3, 9 -12). In cultured cells, T-cad has been shown to be expressed in cardiomyocytes, fibroblasts, epithelial cells, neuronal cells and vascular smooth muscle cells (SMC) (6,9,10,13). T-cad expression is significantly reduced in epithelial breast cancer tissue and in various (tumor) cell lines (10), and inactivation of the human T-cad gene in human lung cancer was recently reported (14).…”

mentioning

confidence: 99%

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

Niermann

Kern

Erné

et al. 2000

Biochemical and Biophysical Research Communications

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confidence: 99%

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

Niermann

Kern

Erné

et al. 2000

Biochemical and Biophysical Research Communications

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“…17 Finally, FGF-2 and other growth factors such as PDGF-BB, EGF and IGF downmodulate T-cadherin levels in a dose-and time-dependent fashion. 18 These observations suggest that cell-cell adhesion proteins are common targets for various growth factors; their effects are most likely tissue-specific and cadherin-specific.We previously demonstrated that both the expression of Ecadherin and catenins and the assembly of the complex are altered in pancreatic adenocarcinoma cell lines, with a subsequent impairment of the functionality of the system. We also demonstrated that FGF-1 and FGF-2 enhance E-cadherin-mediated cell-cell adhesion and decrease the in vitro invasion in these cell lines.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma

El‐Hariry¹,

Pignatelli

Lemoine

2001

Int. J. Cancer

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E-cadherin is a transmembrane protein that mediates Ca 2؉ -dependent cell-cell adhesion and is implicated in a number of biologic processes, including cell growth and differentiation, cell recognition and cell sorting during development. We have previously demonstrated that both cell-cell adhesion and invasion are modulated by fibroblast growth factor (FGF)-1 and FGF-2 in a panel of pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF). Here, we examine further the role of FGFs in the expression and activation of the E-cadherin/catenin system. We demonstrate that both FGF-1 and FGF-2 upregulate E-cadherin and ␤-catenin at the protein level in the BxPc3 and HPAF cell lines and modestly in T3M4 cells. FGF-1 and FGF-2 facilitate the association of E-cadherin and ␣-catenin with the cytoskeleton, as demonstrated by the increase in the detergent-insoluble fraction of E-cadherin in BxPc3 and HPAF cells. Since the correct function of the E-cadherin/catenin complex requires its association with the cytoskeleton, our data suggest that FGF-1 and FGF-2 contribute to the integrity and thus the function of the complex. Furthermore, FGFs facilitate the assembly of the E-cadherin/catenin axis. The effect is associated with elevation of tyrosine phosphorylation of E-cadherin, ␣-catenin, ␤-4051catenin and ␥-catenin, but not p120 ctn . These findings indicate that the E-cadherin/catenin system is a target of the FGF/FGFR system and that coordinated signals from both systems may determine the ultimate biologic responses. © 2001 Wiley-Liss, Inc. Key words: E-cadherin; catenins; FGF; FGFR; pancreatic adenocarcinomaEvidence is compelling that a loss of function of E-cadherin and/or one or more of the associated catenins contributes to increased proliferation, invasion and metastasis in a wide variety of solid tumours. 1 Supporting observations include an inverse correlation between E-cadherin expression and increased invasiveness in vitro, 2 as well as an association between loss of E-cadherin expression and dedifferentiation, advanced tumour grade, metastasis and shortened survival. 3,4 The integrity of the entire E-cadherin-catenin-actin network is indispensable for E-cadherin-mediated cell-cell adhesion. Posttranslational modification such as tyrosine phosphorylation is widely recognised as the prevalent mechanism in regulating cadherin/catenin expression and/or function. 5 The catenins (␤-catenin, ␥-catenin and p120 ctn ) are the major targets of protein tyrosine kinases, which are heavily tyrosine phosphorylated in Src-transformed cells 6 and in response to growth factors such as EGF, 7,8 TGF-␣, PDGF 9,10 and HGF. 11 Furthermore, ␤-catenin and ␥-catenin directly associate with at least two receptor tyrosine kinases: EGFR 7 and c-erbB-2. 12 There is mounting evidence that E-cadherin expression can be modulated, either positively or negatively, by growth factors and cytokines. However, the mechanism of regulation of expression remains largely speculative. For instance, TGF-␤ induces dedifferentiation of normal mammary epithel...

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“…33 Another study on vascular smooth muscle cells reported downmodulation of T-cadherin protein in response to growth factors such as platelet-derived growth factor, epidermal growth factor or insulin-like growth factor, but transcriptional mechanisms were not investigated. 34 In endothelial cells, a requirement of thioredoxin-1 in redox-sensitive modulation of T-cadherin expression was described and a thioredoxin-1-regulated region between À 156 and À 203 bp upstream of the translational start site of CDH13 was identified. 25 In osteosarcoma cells, analysis of the 1500 bp proximal 5 0 -flanking region of CDH13 identified potential binding sites/consensus sequences for several transcription factors, including AHR, the glucocorticoid receptor, progesterone receptor and estradiol receptor.…”

Section: Discussionmentioning

confidence: 99%

BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells

Ellmann

Joshi

Resink

et al. 2012

Laboratory Investigation

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T-cadherin (cadherin 13, H-cadherin, gene name CDH13) has been proposed to act as a tumor-suppressor gene as its expression is significantly diminished in several types of carcinomas, including melanomas. Allelic loss and promoter hypermethylation have been proposed as mechanisms for silencing of CDH13. However, they do not account for loss of T-cadherin expression in all carcinomas, and other genetic or epigenetic alterations can be presumed. The present study investigated transcriptional regulation of CDH13 in melanoma. Bioinformatical analysis pointed to the presence of known BRN2 (also known as POU3F2 and N-Oct-3)-binding motifs in the CDH13 promoter sequence. We found an inverse correlation between BRN2 and T-cadherin protein and transcript expression. Reporter gene analysis and electrophoretic mobility shift assays in melanoma cells demonstrated that CDH13 is a direct target of BRN2 and that BRN2 is a functional transcriptional repressor of CDH13 promoter activity. The regulatory binding element of BRN2 was located À 219 bp of the CDH13 promoter proximal to the start codon and was identified as 5 0 -CATGCAAAA-3 0 . Ectopic expression of BRN2 in BRN2-negative/T-cadherin-positive melanoma cells resulted in suppression of CDH13 promoter activity, whereas BRN2 knockdown in BRN2-positive/T-cadherin-negative melanoma cells resulted in re-expression of T-cadherin transcripts and protein. Transcriptional repression of CDH13 by BRN2 may participate in malignant transformation of melanoma by increasing invasion and migration potentials of melanoma cells. The study has identified CDH13 as a novel direct BRN2 transcriptional target gene and has advanced knowledge of mechanisms underlying loss of T-cadherin expression in melanoma.

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Characteristics of Smooth Muscle Cell Lipoprotein Binding Proteins (p105/p130) as T-Cadherin and Regulation by Positive and Negative Growth Regulators

Cited by 25 publications

References 35 publications

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

The Glycosyl Phosphatidylinositol Anchor of Human T-Cadherin Binds Lipoproteins

FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma

BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells

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