E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.

Hülsken, Jörg; Birchmeier, Walter; Behrens, Jürgen

doi:10.1083/jcb.127.6.2061

Cited by 593 publications

(391 citation statements)

References 54 publications

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“…The core of the pathway is the stability of b-catenin, a protein that plays a dual role in intercellular junction formation and transcriptional regulation (Hulsken et al 1994;Behrens et al 1996;Nelson and Nusse 2004). Indeed, b-catenin was first characterized as an adherens junction protein, which, through its Armadillo repeats, binds to the core transmembrane adhesion protein Ecadherin and, through its N-terminal domain, associates with a-catenin, a protein that binds actin and other actinregulators.…”

Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

2014

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In mammals, Wnt/b-catenin signaling features prominently in stem cells and cancers, but how and for what purposes have been matters of much debate. In this review, we summarize our current knowledge of Wnt/b-catenin signaling and its downstream transcriptional regulators in normal and malignant stem cells. We centered this review largely on three types of stem cells-embryonic stem cells, hair follicle stem cells, and intestinal epithelial stem cells-in which the roles of Wnt/b-catenin have been extensively studied. Using these models, we unravel how many controversial issues surrounding Wnt signaling have been resolved by dissecting the diversity of its downstream circuitry and effectors, often leading to opposite outcomes of Wnt/b-catenin-mediated regulation and differences rooted in stage-and context-dependent effects.

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Section: Overview Of Wnt Signaling Pathwaysmentioning

confidence: 99%

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

2014

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“…Early studies identified E-cadherin/catenin interactions as imperative for cell -cell adhesion (Chitaev and Troyanovsky, 1998). b-Catenin binds with high affinity to the carboxyl-terminal region of the cadherin cytoplasmic tail, while a-catenin serves as an anchor, by bridging to aactinin, to link the complex to the actin cytoskeleton (Aberle et al, 1994;Hulsken et al, 1994;Funayama et al, 1995;Jou et al, 1995;Rimm et al, 1995). These molecules not only play structural roles but also alter cell responses and phenotypes.…”

mentioning

confidence: 99%

“…These molecules not only play structural roles but also alter cell responses and phenotypes. b-Catenin is also found to immunoprecipitate with the APC tumour suppressor protein (Su et al, 1993;Hulsken et al, 1994;Shibata et al, 1994), and has been recently identified as an oncogene (Kim et al, 2002;Minamoto et al, 2002;Kielhorn et al, 2003;Schneider et al, 2003). It is also central to cell signalling, as upon dissociation from E-cadherin, it transits to the nucleus to alter transcriptional profiles (Mason et al, 2002;van de Wetering et al, 2002).…”

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confidence: 99%

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

2005

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Cetrorelix, a luteinising hormone-releasing hormone (LHRH) analogue, has been shown to limit growth of the human androgenindependent prostate cell line DU-145, although other inhibitory actions may also be affected. Both growth and invasion of DU-145 cells are linked to autocrine epidermal growth factor receptor (EGFR) signalling. Invasiveness requires not only cells to migrate to conduits, but also reduced adhesiveness between tumour cells to enable separation from the tumour mass. Thus, we investigated whether Cetrorelix alters the DU-145 cell -cell adhesion and if this occurs via altered EGFR signalling. Pharmacologic levels of Cetrorelix limited the invasiveness of a highly invasive DU-145 subline overexpressing full-length EGFR (DU-145 WT). Extended exposure of the cells to Cetrorelix resulted in increased levels of the cell -cell adhesion complex molecules E-cadherin, a-and bcatenin, and p120. Puromycin blocked the increases in E-cadherin and b-catenin levels, suggesting that de novo protein synthesis is required. The Cetrorelix effect appears to occur via transmodulation of EGFR by a protein kinase C (PKC)-dependent mechanism, as there were no changes in DU-145 cells expressing EGFR engineered to negate the PKC transattenuation site (DU-145 A654); downregulation of EGFR signalling produced a similar upregulation in adhesion complex proteins, further suggesting a role for autocrine signalling. Cetrorelix increased the cell -cell adhesiveness of DU-145 WT cells to an extent similar to that seen when autocrine EGFR signalling is blocked; as expected, DU-145 A654 cell -cell adhesion also was unaffected by Cetrorelix. The increased adhesiveness is expected as the adhesion complex molecules moved to the cells' periphery. These data offer direct insight into the possible crosstalk pathways between the LHRH and EGFR receptor signalling. The ability of Cetrorelix to downregulate EGFR signalling and subsequently reverse the antiadhesiveness found in metastatic prostate cancer highlights a novel potential target for therapeutic strategies.

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“…9,10 Normal cells have little free ␤-catenin proteins, and most of them are bound to cadherin. The rest form the complex with APC (adenomatous polyposis coli) gene products and glycogen synthetase kinase-3␤ (GSK-3␤).…”

mentioning

confidence: 99%

Tumor heterogeneity in small hepatocellular carcinoma: Analysis of tumor cell proliferation, expression and mutation of p53 AND ?-catenin

Matsuda

Fujii

et al. 2001

Int. J. Cancer

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Most hepatocellular carcinomas (HCCs) first occur as welldifferentiated HCCs, from which poorly differentiated HCC cells develop because of dedifferentiation. In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation-related genes p53 and ␤-catenin. Of 41 surgically resected small HCCs, 11 were identified to have tumor heterogeneity. DNA from the 11 small HCCs, consisting of 29 intratumoral lesions and 11 noncancerous liver tissues adjacent to HCCs, was extracted from paraffin embedded tissue sections. Exons 5-8 of p53 gene and exon 3 of ␤-catenin gene were amplified by polymerase chain reaction and analyzed by direct sequence. The serial sections were also immunostained by anti-Ki-67, p53 and ␤-catenin antibody. Immunohistochemistry showed that the p53 overexpression was significantly related to the proliferative activities as evaluated by Ki-67 immunostaining and to the histological differentiation. The expression of ␤-catenin was found to be heterogeneously distributed not only in various histological grades of the same tumor but also in areas of the same histological grade. p53 and ␤-catenin gene mutations were detected in 1 tumor respectively, both of which were second primary HCCs and also recurred later. The p53 mutation showed the same mutation pattern in heterogeneous subpopulations. ␤-catenin mutation was detected only in the less differentiated lesion but not in the well-differentiated lesion of tumor. In conclusion, our findings suggest that there was histological heterogeneity in small but established HCC, which was accompanied by increased proliferative activity and p53 overexpression. The overexpression of ␤-catenin may be related to the proliferative activity and dedifferentiation of HCC.

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E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.

Cited by 593 publications

References 54 publications

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

Wnt some lose some: transcriptional governance of stem cells by Wnt/β-catenin signaling

Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline

Tumor heterogeneity in small hepatocellular carcinoma: Analysis of tumor cell proliferation, expression and mutation of p53 AND ?-catenin

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