p120cat delocalization in cell lines of oral cancer

Muzio, Lorenzo Lo; Pannone, Giuseppe; Staibano, S.; Mignogna, Michele Davide; Serpico, Rosario; Fanali, S; Rosa, Gaetano De; Piattelli, Adriano; Mariggiò, Maria Addolorata

doi:10.1016/s1368-8375(01)00027-6

Cited by 18 publications

(19 citation statements)

References 78 publications

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“…Our results indicate, however, that the nuclear translocation of p120 ctn does not cause or stimulate the branching phenotype. It is noteworthy that recent studies have observed increased nuclear localization of p120 ctn in cancers of the pancreas (Mayerle et al, 2003) and mouth (Muzio et al, 2002), and in colorectal polyps (Valizadeh et al, 1997). This is consistent with the fact that decreased cadherin expression, a frequent observation in human cancers, leaves p120 ctn stranded in the cytosol (Roczniak-Ferguson and Reynolds, 2003;van Hengel et al, 1999) and perhaps competent for nuclear translocation.…”

Section: Nls-regulated Nuclear Localization Of P120 Ctnmentioning

confidence: 98%

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

Kelly

Spring

Otchere

et al. 2004

Journal of Cell Science

104

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IntroductionThe Armadillo catenins, β-, γ-and p120 ctn , are multifunctional proteins whose malfunction contributes to tumor progression by various means (Behrens, 1999;Van Aken et al., 2001). They are members of a larger family of Armadillo proteins that are characterized by the presence of an Armadillo domain consisting of ten or more tandem copies of a 42 amino-acid Armadillo repeat (Peifer et al., 1994). The importance of the Armadillo catenins in tumorigenesis was first credited to their involvement in the multiprotein cadherin-catenin complex, which forms the major cell-cell adhesion system in epithelial cells. Dysfunction of this complex, through defects in any of its components, correlates with the metastatic phenotype iñ 50% of human carcinomas (Behrens, 1999;Yap, 1998). The key participant in this complex is the transmembrane glycoprotein and tumor suppressor E-cadherin that mediates cell-cell adhesion by the homophilic interactions of its extracellular domain. E-cadherin is then anchored to the underlying actin cytoskeleton by the classical catenin cofactors, β-and γ-catenin, that bind E-cadherin in a mutually exclusive manner (reviewed by Nollet et al., 1999). These classical catenins bind simultaneously to a highly conserved carboxy-terminal domain of E-cadherin and to the actinbinding protein α-catenin (reviewed by Behrens, 1999;Rimm et al., 1995). Like β-and γ-catenin, the nonclassical Armadillo catenin p120 ctn binds the cytoplasmic tail of E-cadherin via its Arm domain Reynolds et al., 1992). However, β-and γ-catenin compete for binding to the distal conserved catenin-binding domain, and function by anchoring E-cadherin to the actin cytoskeleton, whereas p120 ctn binds Ecadherin at a distinct juxtamembrane domain (JMD) and does not interact with α-catenin (Daniel and Reynolds, 1995;Thoreson et al., 2000). Importantly, the JMD is implicated in E-cadherin stability (Ireton et al., 2002;Pettitt et al., 2003), modulating cadherin adhesive strength (Aono et al., 1999;Ohkubo and Ozawa, 1999;Thoreson et al., 2000;Yap et al., 1998) and regulating cytoskeletal dynamics Grosheva et al., 2001;Noren et al., 2000), and as such p120 ctn is speculated to be a key mediator of these effects. This hypothesis is supported by recent observations that p120 ctn modulates the activities of RhoA, Rac and Cdc42, which are key mediators of cytoskeletal organization Grosheva et al., 2001;Noren et al., 2000).Originally identified as a Src kinase substrate (Reynolds et al., 1989), it was the structural similarity of p120 ctn to β-catenin that led to the discovery of p120 ctn as a novel catenin component of the cadherin complex (Daniel and Reynolds, 2675The Armadillo catenin p120 ctn regulates cadherin adhesive strength at the plasma membrane and interacts with the novel BTB/POZ transcriptional repressor Kaiso in the nucleus. The dual localization of p120 ctn at cell-cell junctions and in the nucleus suggests that its nucleocytoplasmic trafficking is tightly regulated. Here we report on the identification of a specific and h...

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Section: Nls-regulated Nuclear Localization Of P120 Ctnmentioning

confidence: 98%

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

Kelly

Spring

Otchere

et al. 2004

Journal of Cell Science

104

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“…Catenin delocalization has been reported in pre-malignant lesions of the oral cavity and in OSCC (21)(22)(23). In previous studies, we have reported that the distribution of ß-catenin is different in OSCC cells than in normal mucosal cells.…”

Section: Discussionmentioning

confidence: 70%

“…Previous studies have shown that APC. CTNNB1 and Axin are frequently mutated in different types of human cancers (16), as well as colorectal cancer, gastric cancer, liver cancer and pancreatic neoplasia; however, mutations in APC or CTNNB1 are rarely found in OSCC cell lines and in OSCC (21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

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WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors

Caraglia¹

2010

Oncol Rep

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Abstract. Epigenetic DNA methylations plays an important role in oral carcinogenesis. The soluble frizzled receptor protein (SFRP) family together with WIF-1 and DKK-3 encodes antagonists of the WNT pathway. Silencing of these genes leads to constitutive WNT signalling. Because aberrant expression of ß-catenin might be associated with the epigenetic inactivation of WNT inhibitors, we analyzed, in a collection of primary OSCC with matched normal oral mucosa, the methylation status of a complete panel of genes, SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3, that are involved directly and indirectly in WNT pathway, in order to demonstrate WNT-pathway activation in the absence of ß-catenin and/or APC/Axin mutations during oral carcinogenesis. Methylation-specific PCR (MSP) was performed to study inactivation of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes in 37 cases of paraffin embedded oral cancer. This study showed that the methylation is an important epigenetic alteration in oral cancer. In particular, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 revealed methylation status of their promoter in OSCC, whereas SFRP-1 showed demethylation in cancer. Fisher's exact test revealed statistically significant results (p<0.05) for all genes. The Wald test confirmed the statistically significant association between SFRP2-4-5 gene methylation and OSCC (p<0.05). SFRP-1 was also characterized by a different statistically significant epigenetic behaviour, because of it was demethylated in cancer (p<0.05). Statistical regression test showed high levels of sensitivity, specificity and accuracy for SFRP genes, while WIF-1 and DKK-3 have reportedly high specificity, moderate accuracy but low sensitivity. This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP, WIF-1 and DKK-3 genes.

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“…The loss or mislocalization of p120 ctn correlates with poor patient prognoses of carcinomas of the colon, bladder, stomach, breast, prostate, lung and pancreas (Thoreson & Reynolds, 2002). Cytoplasmic mislocation of p120 ctn in oral carcinoma cell lines, while it is localized at the cell membrane of normal oral keratinocytes, was reported previously (Lo Muzio et al, 2002). However, the loss of expression in the epidermis does not have an obvious effect on cell-cell adhesion but reduces expression level of E-cadherin.…”

Section: Loss Of E-cadherin Expression In Oral Squamous Cell Carcinomasmentioning

confidence: 62%

Cadherin Expression and Progression of Squamous Cell Carcinomas of the Oral Cavity

Imai¹,

Maeda²,

Chiba³

2012

Squamous Cell Carcinoma

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p120cat delocalization in cell lines of oral cancer

Cited by 18 publications

References 78 publications

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

NLS-dependent nuclear localization of p120ctnis necessary to relieve Kaiso-mediated transcriptional repression

WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors

Cadherin Expression and Progression of Squamous Cell Carcinomas of the Oral Cavity

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