Kaiso Represses the Cell Cycle Gene cyclin D1 via Sequence-Specific and Methyl-CpG-Dependent Mechanisms

Donaldson, Nickett S.; Pierre, Christina C.; Anstey, Michelle I.; Robinson, Shaiya C.; Weerawardane, Sonali; Daniel, Juliet M.

doi:10.1371/journal.pone.0050398

Cited by 41 publications

(57 citation statements)

References 23 publications

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“…Several putative KBS-containing genes have been identified 45,79–81 (see below). Although this limited number does not indicate larger roles for Kaiso in conjunction with p120 catenin, surprising findings have arisen.…”

Section: Nuclear Roles Of Kaiso and P120 Cateninmentioning

confidence: 99%

Beyond β-catenin: prospects for a larger catenin network in the nucleus

McCrea

Gottardi

2015

Nat Rev Mol Cell Biol

120

108

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β-catenin is widely regarded as the primary transducer of canonical WNT signals to the nucleus. In most vertebrates, there are eight additional catenins that are structurally related to β-catenin, and three α-catenin genes encoding actin-binding proteins that are structurally related to vinculin. Although these catenins were initially identified in association with cadherins at cell–cell junctions, more recent evidence suggests that the majority of catenins also localize to the nucleus and regulate gene expression. Moreover, the number of catenins reported to be responsive to canonical WNT signals is increasing. Here, we posit that multiple catenins form a functional network in the nucleus, possibly engaging in conserved protein–protein interactions that are currently better characterized in the context of actin-based cell junctions.

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Section: Nuclear Roles Of Kaiso and P120 Cateninmentioning

confidence: 99%

Beyond β-catenin: prospects for a larger catenin network in the nucleus

McCrea

Gottardi

2015

Nat Rev Mol Cell Biol

120

108

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“…p120-catenin in cancer 3517 p120 can modulate gene expression through its direct interaction with the transcriptional repressor Kaiso (ZTBT33) (Daniel and Reynolds, 1999). Kaiso is a member of the POZ-ZF or BTB family of transcription factors that can bind to methylated DNA and/or a specific Kaiso binding sequence (TCCTGCNA) (Prokhortchouk et al, 2001;Daniel et al, 2002;Daniel, 2007;Donaldson et al, 2012). Binding of p120 to Kaiso might inhibit its DNA binding and relieve the repression of its target genes, such as WNT11, CyclinD1 (CCND1) and MMP7, which have been linked to noncanonical and canonical WNT-dependent developmental processes (Daniel et al, 2002;Kim et al, 2004;Park et al, 2006;Hong et al, 2010).…”

Section: Nuclear Localization and Regulation Of Transcriptional Activmentioning

confidence: 99%

p120-catenin in cancer – mechanisms, models and opportunities for intervention

Schackmann

Tenhagen

Ven

et al. 2013

Journal of Cell Science

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The epithelial adherens junction is an E-cadherin-based complex that controls tissue integrity and is stabilized at the plasma membrane by p120-catenin (p120, also known as CTNND1). Mutational and epigenetic inactivation of E-cadherin has been strongly implicated in the development and progression of cancer. In this setting, p120 translocates to the cytosol where it exerts oncogenic properties through aberrant regulation of Rho GTPases, growth factor receptor signaling and derepression of Kaiso (also known as ZBTB33) target genes. In contrast, indirect inactivation of the adherens junction through conditional knockout of p120 in mice was recently linked to tumor formation, indicating that p120 can also function as a tumor suppressor. Supporting these opposing functions are findings in human cancer, which show that either loss or cytoplasmic localization of p120 is a common feature in the progression of several types of carcinoma. Underlying this dual biological phenomenon might be the context-dependent regulation of Rho GTPases in the cytosol and the derepression of Kaiso target genes. Here, we discuss past and present findings that implicate p120 in the regulation of cancer progression and highlight opportunities for clinical intervention.

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“…In other models, Kaiso regulated genes associated with EMT, including E-cadherin [16, 18], Wnt 11 [19], and matrilysin [20]. However, with the exception of Kaiso-regulated expression of cyclin D1 [21], a tumor promoting function for Kaiso in breast cancer has yet to be elucidated. During preparation of this manuscript, a report was published demonstrating that increased expression of Kaiso, in particular its nuclear localization, is associated with high-grade, triple-negative IDCs [22], suggesting that Kaiso promotes aggressive breast tumors.…”

Section: Introductionmentioning

confidence: 99%

Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas

Jones

Wang

Karanam

et al. 2014

Clin Exp Metastasis

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The expression and biological consequences of Kaiso, a novel bi-modal transcription factor, in infiltrating ductal carcinomas (IDCs) have not been widely investigated. In the present study, we determined Kaiso expression and subcellular localization in 146 normal tissues, 376 IDCs, and 85 lymph node metastases. In IDCs, there was higher Kaiso expression in both the cytoplasmic and nuclear compartments, which correlated with age <48 (cytoplasmic p<0.0093; nuclear p< 0.0001) and moderate differentiation (cytoplasmic p<0.0042; nuclear p<0.0001), as determined by Chi-square analysis. However, only nuclear Kaiso correlated with poor prognostic factors, i.e., race (African Americans) (p<0.0001), poor differentiation (p<0.0001), and metastases (p<0.0001). Nuclear Kaiso was also associated with worse overall survival (p<0.0019), with African American patients displaying worse survival rates relative to Caucasian patients (p<0.029). MCF-7 (non-metastatic), MDA-MB-468 (few metastases), and MDA-MB-231 (highly metastatic) breast cancer cells demonstrated increasing Kaiso levels, with more nuclear localization in the highly metastatic cell line. Over-expression of Kaiso in MCF-7 cells increased cell migration and invasion, but treatment of MDA-MB-468 and MDA-MB-231 cells with si-Kaiso decreased cell migration and invasion and induced expression of E-cadherin RNA and protein. E-cadherin re-expression was associated with a reversal of mesenchymal associated cadherins, N-cadherin and cadherin 11, as well as decreased vitmenin expression. Further, Kaiso directly bound to methylated sequences in the E-cadherin promoter, an effect prevented by 5-aza-2-deoxycytidine. Immunofluorescence co-staining of poorly differentiated IDCs demonstrated that nuclear Kaiso is associated with a loss of E-cadherin expression. These findings support a role for Kaiso in promoting aggressive breast tumors.

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Kaiso Represses the Cell Cycle Gene cyclin D1 via Sequence-Specific and Methyl-CpG-Dependent Mechanisms

Cited by 41 publications

References 23 publications

Beyond β-catenin: prospects for a larger catenin network in the nucleus

Beyond β-catenin: prospects for a larger catenin network in the nucleus

p120-catenin in cancer – mechanisms, models and opportunities for intervention

Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas

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