Exogenous Expression of β-Catenin Regulates Contact Inhibition, Anchorage-Independent Growth, Anoikis, and Radiation-Induced Cell Cycle Arrest

Orford, Keith; Orford, Caroline C.; Byers, Stephen W.

doi:10.1083/jcb.146.4.855

Cited by 252 publications

(206 citation statements)

References 60 publications

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“…Overexpression of β-catenin, due to genetic alterations of the β-catenin and APC (adenomatous polyposis coli) genes in cancer cells is known to play an important role in tumorigenesis [6]. However, it has also been reported that ectopically overexpressed β-catenin stimulates cell growth in the presence, but not in the absence, of serum [32,33]. Therefore, the physiological level of β-catenin increased by Wnt-3a may co-operate with other factors in the serum to stimulate cell growth.…”

Section: Activities Of Wnt-5amentioning

confidence: 99%

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Kurayoshi

Yamamoto

Izumi

et al. 2007

Biochemical Journal

205

215

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Wnt-5a is a representative ligand that activates a β-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys 104 and glycans at Asn 114 , Asn 120 , Asn 311 and Asn 325 . The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent Tcell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.

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Section: Activities Of Wnt-5amentioning

confidence: 99%

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Kurayoshi

Yamamoto

Izumi

et al. 2007

Biochemical Journal

205

215

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“…However, it has become apparent that the cell cycle and WNT signaling are intrinsically linked (16). In a seminal study, WNT-␤-catenin signaling (and ␤-catenin protein levels) were noted to oscillate during the cell cycle, peaking at the G 2 /M transition (17). Since that initial observation, many of the components of the WNT pathway have been shown to play an integral role during cell division.…”

mentioning

confidence: 99%

Human SMC2 Protein, a Core Subunit of Human Condensin Complex, Is a Novel Transcriptional Target of the WNT Signaling Pathway and a New Therapeutic Target

Dávalos

Suárez-López

Castaño

et al. 2012

Journal of Biological Chemistry

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Background: Condensin SMC proteins are frequently overexpressed in WNT-activated hyperplastic cells. Results:The SMC2 promoter is a novel target on the ␤-catenin⅐TCF4 transcription complex. Conclusion: ␤-Catenin⅐TCF4 may drive production of condensin in hyperplastic cells. SMC2 is required to ensure cellular mitosis and fast proliferation. Significance: Down-regulation of SMC2 expression can repress cell proliferation in WNT-activated cells and represents a new therapeutic target in cancer treatment.

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“…This property of cancer cells has served as a 'golden standard' for cell transformation for three decades (Freedman and Shin, 1974). Second, expression of oncogenes, such as ras (Rak et al, 1995), b-catenin (Orford et al, 1999), epidermal growth factor receptor and ErbB2 (Reginato et al, 2003) in nonmalignant epithelial cells is known to render these cells anoikis-resistant. Third, loss of oncogenes, such as ras, by carcinoma cells was shown to block their in vivo tumorigenicity and anoikis resistance (Rosen et al, 2000;Liu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells

Liu

et al. 2006

Oncogene

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Detachment of normal epithelial cells from the extracellular matrix triggers apoptosis, a phenomenon called anoikis. Conversely, carcinoma cells tend to be relatively more anoikis-resistant than their normal counterparts, and this increased resistance represents a critical feature of the malignant phenotype. Mechanisms that control susceptibility and resistance to anoikis are not fully understood. It is now known that detachment of non-malignant epithelial cells triggers both pro-and antiapoptotic signals, and it is the balance between these signals and the duration of detachment that determine further fate of the cells. Detachment-induced antiapoptotic events delay anoikis and if cells reattach relatively soon after detachment they survive. Direct regulators of apoptosis responsible for this delay of anoikis are unknown. We found that detachment of non-malignant intestinal epithelial cells triggers upregulation of inhibitors of apoptosis protein (IAP) family, such as X-chromosome-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis-2 (cIAP2). We demonstrated that this upregulation requires detachmentdependent activation of the transcription factor nuclear factor-jB. We further observed that various IAP antagonists accelerate anoikis, indicating that upregulation of the IAPs delays detachment-triggered apoptosis. We conclude that the IAPs are important regulators of the balance between detachment-triggered life and death signals. Perhaps, not by coincidence, these proteins are often upregulated in carcinomas, tumors composed of cells that tend to be anoikis-resistant.

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Exogenous Expression of β-Catenin Regulates Contact Inhibition, Anchorage-Independent Growth, Anoikis, and Radiation-Induced Cell Cycle Arrest

Cited by 252 publications

References 60 publications

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Human SMC2 Protein, a Core Subunit of Human Condensin Complex, Is a Novel Transcriptional Target of the WNT Signaling Pathway and a New Therapeutic Target

Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells

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