Zeppo1 is a novel metastasis promoter that represses<i>E-cadherin</i>expression and regulates p120-catenin isoform expression and localization

Slorach, Euan M.; Chou, Jonathan; Werb, Zena

doi:10.1101/gad.1998111

Cited by 85 publications

(112 citation statements)

References 65 publications

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“…TGF-b was also shown to induce invadopodia formation in EpH4 and MCF10A mammary epithelial cells through up-regulation of Twist1 (Eckert et al 2011) and the focal adhesion protein Hic-5 (Pignatelli et al 2012) to promote matrix degradation and invasion. Furthermore, Zeppo1, a novel metastasis promoter that can repress E-cadherin expression, was found to induce EpH4.9 cells to form invadopodia-like structures in three dimensions (Slorach et al 2011). Together, these studies suggest that the EMT program not only allows carcinoma cells to dissociate from each other but also provides them the ability to degrade ECM for single-cell invasion to initiate the metastatic cascade (Fig.…”

Section: Degradation Of the Ecmmentioning

confidence: 75%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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Tumor metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. Metastasis occurs through a series of steps: local invasion, intravasation, transport, extravasation, and colonization. A developmental program termed epithelial-mesenchymal transition (EMT) has been shown to play a critical role in promoting metastasis in epithelium-derived carcinoma. Recent experimental and clinical studies have improved our knowledge of this dynamic program and implicated EMT and its reverse program, mesenchymal-epithelial transition (MET), in the metastatic process. Here, we review the functional requirement of EMT and/or MET during the individual steps of tumor metastasis and discuss the potential of targeting this program when treating metastatic diseases.Epithelial and mesenchymal cell types have long been recognized by their unique cell morphology and organization in tissues. Epithelial cells form polarized sheets or layers of cells that are connected laterally via several types of cellular junctions, including adherens junctions, desmosomes, and tight junctions. In addition, epithelial cells anchor themselves to the underlying basement membrane via hemidesmosomes to maintain apical-basal polarity. Both desmosomes and hemidesmosomes further connect with the epithelial-specific cytokeratin intermediate filaments. In contrast, mesenchymal cells embed themselves inside the extracellular matrix (ECM) and rarely establish tight contact with neighboring cells. During specific embryonic morphogenesis processes such as mesoderm formation and neural crest development, epithelial cells can exhibit enormous plasticity and transit into a mesenchymal state by activating the epithelial-mesenchymal transition (EMT) program. After EMT, these cells lose their epithelial junctions and switch to producing vimentin filaments. The functional hallmark of the EMT program is to allow stationary epithelial cells to gain the ability to migrate and invade during developmental morphogenesis (Boyer and Thiery 1993;Hay 1995).Although epithelial cells convert into the mesenchymal state during developmental EMT, entering the EMT program is not necessarily an irreversible commitment, as evident during kidney tubule formation. These epithelial cells can activate a transitory EMT program and then undergo a reverse process called mesenchymal-epithelial transition (MET) to continue their differentiation paths (Thiery et al. 2009;Lim and Thiery 2012). In many instances, the identification of an epithelial versus a mesenchymal state can be relatively fluid, and a partial EMT/MET frequently occurs to fulfill unique developmental tasks. These dynamic EMT/MET events highlight the enormous flexibility of presumably differentiated cells during morphogenesis.In the past decade, an increasing number of studies have provided strong evidence for the reinitiation of the EMT developmental program in carcinoma progression and metastasis. This EMT program in tumor metastasis possesses many morpholog...

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Section: Degradation Of the Ecmmentioning

confidence: 75%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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“…Several authors have reported that the cell proliferation was promoted in a p120 siRNA stable-transfected NIH3T3 cell line (Wildenberg et al, 2006), in the keratinocytes of p120 conditional-knockout mouse (PerezMoreno et al, 2006;Perez-Moreno et al, 2008) by activation of RhoA signaling. Such an effect of p120 might be reversely linked to E-cadherin or isoform 1A of p120 at the cell membrane (Slorach et al, 2011;Soto et al, 2008). However, others have demonstrated that the growth of MDA-MB-231 cells was promoted by p120 (Soto et al, 2008) or the growth of single MDCK cells was inhibited by p120 knockdown (Dohn et al, 2009).…”

Section: Discussionmentioning

confidence: 98%

Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions

Zhu

Chen

et al. 2012

Journal of Cell Science

160

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SummaryContact inhibition ubiquitously exists in non-transformed cells that are in contact with neighboring cells. This phenomenon explains the poor regenerative capacity of in vivo human corneal endothelial cells during aging, injury and surgery. This study demonstrated that the conventional approach of expanding human corneal endothelial cells by disrupting contact inhibition with EDTA followed by bFGF activated canonical Wnt signaling and lost the normal phenotype to endothelial-mesenchymal transition, especially if TGFb1 was added. By contrast, siRNA against p120 catenin (CTNND1) also uniquely promoted proliferation of the endothelial cells by activating trafficking of p120 catenin to the nucleus, thus relieving repression by nuclear Kaiso. This nuclear p120-catenin-Kaiso signaling is associated with activation of RhoA-ROCK signaling, destabilization of microtubules and inhibition of Hippo signaling, but not with activation of Wnt-b-catenin signaling. Consequently, proliferating human corneal endothelial cells maintained a hexagonal shape, with junctional expression of N-cadherin, ZO-1 and Na + /K + -ATPase. Further expansion of human corneal endothelial monolayers with a normal phenotype and a higher density was possible by prolonging treatment with p120 catenin siRNA followed by its withdrawal. This new strategy of perturbing contact inhibition by selective activation of p120-catenin-Kaiso signaling without disrupting adherent junction could be used to engineer surgical grafts containing normal human corneal endothelial cells to meet a global corneal shortage and for endothelial keratoplasties.

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“…Another study found that Ki67 was an important regulator, which played an important role in promoting tumor growth, angiogenesis and invasion (Nakamura et al, 2008). FasL plays an important role in the synergistic effect of tumor immunity (Slorach et al, 2011). A previous study found that various natural killer cells prompted loss of FasL in deprived tumor cells, which suggested that it played a role in inhibiting tumorigenesis (Sobin et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Study on the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma

Sn¹,

Yj²,

Liu³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. This study aimed to investigate the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma and to explore the biological processes and signal pathways related to cervical carcinoma. Cervical carcinoma tissue specimens from 200 patients and normal tissue specimens adjacent to lesions from 30 cases were collected in this study. Ki67 and FasL proteins in these specimens were detected by immunohistochemical methods. A series of statistical methods were carried out to investigate the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma. The expression of Ki67 and FasL in cervical carcinoma tissues was significantly higher than that in normal cervical tissue. The positive rate of Ki67 and FasL increased with the increase in the degree of cervical lesions. There was a positive correlation between the expression of Ki67 and FasL in cervical lesions. The expression of Ki67 and FasL affected the five-year survival rate of postoperative patients. Ki67 and FasL were independent factors for the prognosis of patients with cervical cancer. The expression of Ki67 and FasL is closely related to the occurrence and development of cervical carcinoma. There is a positive correlation between Ki67 and FasL, and they may be biomarkers of cervical cancer.

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Zeppo1 is a novel metastasis promoter that repressesE-cadherinexpression and regulates p120-catenin isoform expression and localization

Cited by 85 publications

References 65 publications

Epithelial–mesenchymal plasticity in carcinoma metastasis

Epithelial–mesenchymal plasticity in carcinoma metastasis

Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions

Study on the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma

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