High Motility of Triple-negative Breast Cancer Cells Is Due to Repression of Plakoglobin Gene by Metastasis Modulator Protein SLUG

Bailey, Charvann K.; Mittal, Mahesh Kumar; Misra, Smita; Chaudhuri, Gautam

doi:10.1074/jbc.m112.345728

Cited by 37 publications

(45 citation statements)

References 47 publications

(122 reference statements)

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“…38 These findings confirm previous studies demonstrating the relevance of plakoglobin expression for metastases in breast and lung carcinomas. [39][40][41] ARE CTCS CAPABLE OF INITIATING METASTASES? CTC capturing systems revealed that aggressive tumors release thousands of cancer cells into the circulation each day, 42-44 yet most patients develop only few metastases, suggesting that metastasis is a highly inefficient process.…”

Section: Active or Passive Entry Of Ctcs Into The Circulationmentioning

confidence: 99%

The biology of circulating tumor cells

2015

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Metastasis is a biologically complex process consisting of numerous stochastic events which may tremendously differ across various cancer types. Circulating tumor cells (CTCs) are cells that are shed from primary tumors and metastatic deposits into the blood stream. CTCs bear a tremendous potential to improve our understanding of steps involved in the metastatic cascade, starting from intravasation of tumor cells into the circulation until the formation of clinically detectable metastasis. These efforts were propelled by novel high-resolution approaches to dissect the genomes and transcriptomes of CTCs. Furthermore, capturing of viable CTCs has paved the way for innovative culturing technologies to study fundamental characteristics of CTCs such as invasiveness, their kinetics and responses to selection barriers, such as given therapies. Hence the study of CTCs is not only instrumental as a basic research tool, but also allows the serial monitoring of tumor genotypes and may therefore provide predictive and prognostic biomarkers for clinicians. Here, we review how CTCs have contributed to significant insights into the metastatic process and how they may be utilized in clinical practice.

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Section: Active or Passive Entry Of Ctcs Into The Circulationmentioning

confidence: 99%

The biology of circulating tumor cells

2015

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“…Suppression of PKC-a or PKC-d isoforms increases Dsg3 expression, whereas suppression of PKC-d and PKC-1 isoforms either decreases or increases Dsg1 levels, respectively (Szegedi et al 2009 (Roemer 2012) and p63 has been shown by chromatin immunoprecipitation (ChIP) to bind and activate Dsg1, Dsc3, and Dp promoters (Ferone et al 2013;Johnson et al 2014). Rho-mediated changes in the actin cytoskeleton lead to changes in Srf-dependent transcription (Miralles et al 2003) and Srf controls the expression of Pkp2 and Dsg1, which in turn drives a program of terminal differentiation (Leitner et al 2011;Dubash et al 2013), The Wnt-regulated TCF/Lef transcription complex has been implicated in regulation of Dsg4, Dsc2, Dsc3, and Pg expression but direct binding of these transcription factors to desmosomal component promoters has only been shown in a few instances (Table 1) (Bazzi et al 2009;Bailey et al 2012;Tokonzaba et al 2013). Pg itself complexes with TCF/ Lef-1 to regulate the balance of Dsc2 and Dsc3 expression (Tokonzaba et al 2013).…”

Section: Transcriptional Regulation Of Desmosomal Componentsmentioning

confidence: 99%

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Johnson

Najor

Green

2014

Cold Spring Harbor Perspectives in Medicine

112

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“…In contrast, plakoglobin has often been associated with tumor/metastasis suppressor activity, although the mechanisms underlying this activity remain unclear. A number of studies have suggested that plakoglobin decreases cell proliferation, migration and invasion and induces apoptosis (Simcha et al, 1996;Parker et al, 1998;Pantel et al, 1998;Charpentier et al, 2000;Winn et al, 2002;Rieger-Christ et al, 2005;Yin et al, 2005;Dusek et al, 2007;Kanazawa et al, 2008;Närkiö-Mäkelä et al, 2009;Todorović et al, 2010;Aktary et al, 2010;Aktary and Pasdar, 2012;Bailey et al, 2012;Holen et al, 2012;Franzen et al, 2012;Lam et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

Aktary

Kulak

Mackey

et al. 2013

Journal of Cell Science

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SummaryPlakoglobin (c-catenin), a constituent of the adherens junction and desmosomes, has signaling capabilities typically associated with tumor/metastasis suppression through mechanisms that remain undefined. To determine the role of plakoglobin during tumorigenesis and metastasis, we expressed plakoglobin in human tongue squamous cell carcinoma (SCC9) cells and compared the mRNA profiles of parental SCC9 cells and their plakoglobin-expressing transfectants (SCC9-PG). We detected several p53-target genes whose levels were altered upon plakoglobin expression. In this study, we identified the p53 regulated tumor suppressor 14-3-3s as a direct plakoglobin-p53 target gene. Coimmunoprecipitation experiments revealed that plakoglobin and p53 interact, and chromatin immunoprecipitation and electrophoretic mobility shift assays revealed that plakoglobin and p53 associate with the 14-3-3s promoter. Furthermore, luciferase reporter assays showed that p53 transcriptional activity is increased in the presence of plakoglobin. Finally, knockdown of plakoglobin in MCF-7 cells followed by luciferase assays confirmed that p53 transcriptional activity is enhanced in the presence of plakoglobin. Our data suggest that plakoglobin regulates gene expression in conjunction with p53 and that plakoglobin may regulate p53 transcriptional activity, which may account, in part, for the tumor/metastasis suppressor activity of plakoglobin.

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High Motility of Triple-negative Breast Cancer Cells Is Due to Repression of Plakoglobin Gene by Metastasis Modulator Protein SLUG

Cited by 37 publications

References 47 publications

The biology of circulating tumor cells

The biology of circulating tumor cells

Desmosomes: Regulators of Cellular Signaling and Adhesion in Epidermal Health and Disease

Plakoglobin interacts with the transcription factor p53 and regulates the expression of 14-3-3σ

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