Reduced PDEF Expression Increases Invasion and Expression of Mesenchymal Genes in Prostate Cancer Cells

Gu, Xuesong; Zerbini, Luiz F.; Otu, Hasan H.; Bhasin, Manoj; Yang, Qian; Joseph, Marie; Grall, Franck; Onatunde, Tomi; Correa, Ricardo G.; Libermann, Towia A.

doi:10.1158/0008-5472.can-06-3689

Cited by 89 publications

(124 citation statements)

References 37 publications

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“…The transcription factor Twist similarly represses E-cadherin expression as well as upregulating N-cadherin levels in prostate cancer cell lines (Kwok et al, 2005;Alexander et al, 2006). In contrast, loss of the epithelium-specific transcription factor prostate-derived ETS factor (PDEF), which is downregulated by TGFb, induces EMT in PC3 cells (Gu et al, 2007). In addition, over-expression of prostate specific antigen (PSA) and kallikrein-related peptidase 4 (KLK4), both potential activators of pro-EGF and latent TGFb2, results in EMT in PC3 cells (Veveris-Lowe et al, 2005;Whitbread et al, 2006).…”

Section: Emt In Prostate Cancermentioning

confidence: 99%

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Hugo

Ackland

Blick

et al. 2007

Journal Cellular Physiology

976

804

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Like a set of bookends, cellular, molecular, and genetic changes of the beginnings of life mirror those of one of the most common cause of death-metastatic cancer. Epithelial to mesenchymal transition (EMT) is an important change in cell phenotype which allows the escape of epithelial cells from the structural constraints imposed by tissue architecture, and was first recognized by Elizabeth Hay in the early to mid 1980's to be a central process in early embryonic morphogenesis. Reversals of these changes, termed mesenchymal to epithelial transitions (METs), also occur and are important in tissue construction in normal development. Over the last decade, evidence has mounted for EMT as the means through which solid tissue epithelial cancers invade and metastasize. However, demonstrating this potentially rapid and transient process in vivo has proven difficult and data connecting the relevance of this process to tumor progression is still somewhat limited and controversial. Evidence for an important role of MET in the development of clinically overt metastases is starting to accumulate, and model systems have been developed. This review details recent advances in the knowledge of EMT as it occurs in breast development and carcinoma and prostate cancer progression, and highlights the role that MET plays in cancer metastasis. Finally, perspectives from a clinical and translational viewpoint are discussed.

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Section: Emt In Prostate Cancermentioning

confidence: 99%

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Hugo

Ackland

Blick

et al. 2007

Journal Cellular Physiology

976

804

View full text Add to dashboard Cite

show abstract

“…Re-expression of PDEF in invasive cells reduces metastatic potential by inhibiting cell migration and invasion in breast and prostate cancer cells (Feldman et al, 2003;Gu et al, 2007;Turner et al, 2007b). The current study used microarray gene expression analysis to identify putative PDEF-regulated target genes that may mediate the observed reduction in metastatic potential.…”

Section: Microarray Analysis Identifies Potential Pdef Transcriptionamentioning

confidence: 99%

“…In breast and other solid tumors, the increased expression of ETS1 and ETS2 (Watabe et al, 1998;Behrens et al, 2001;Buggy et al, 2004Buggy et al, , 2006 as well as PEA3 (Benz et al, 1997;Bosc et al, 2001;Bieche et al, 2004) is associated with increased metastatic potential and an increased ability for motile function through the altered expression of regulatory target genes known to mediate cytoskeletal changes. Prostate derived ETS factor (PDEF) is an epithelial specific ETS family member that is associated with the negative regulation of metastatic potential (Feldman et al, 2003;Ghadersohi et al, 2006;Gu et al, 2007;Turner et al, 2007b). Although PDEF message is sometimes found to be expressed in primary breast and This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08 -02-0154) on June 25, 2008. prostate cancer and has been proposed to be a poor prognosis marker (Nozawa et al, 2000;Ghadersohi and Sood, 2001;Tsujimoto et al, 2002;Ghadersohi et al, 2004), this often does not correlate with protein expression (Nozawa et al, 2000;Tsujimoto et al, 2002;Feldman et al, 2003;Ghadersohi et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Turner

Findlay

Kirven

et al. 2008

MBoC

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Prostate derived ETS factor (PDEF) is an ETS (epithelial-specific E26 transforming sequence) family member that has been identified as a potential tumor suppressor. In multiple invasive breast cancer cells, PDEF expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization. In this study, microarray analysis was used to identify >200 human genes that displayed a common differential expression pattern in three invasive breast cancer cell lines after expression of exogenous PDEF protein. Gene ontology associations and data mining analysis identified focal adhesion, adherens junctions, cell adhesion, and actin cytoskeleton regulation as cell migration-associated interaction pathways significantly impacted by PDEF expression. Validation experiments confirmed the differential expression of four cytoskeleton-associated genes with known functional associations with these pathways: uPA, uPAR, LASP1, and VASP. Significantly, chromatin immunoprecipitation studies identified PDEF as a direct negative regulator of the metastasis-associated gene uPA and phenotypic rescue experiments demonstrate that exogenous urokinase plasminogen activator (uPA) expression can restore the migratory ability of invasive breast cancer cells expressing PDEF. Furthermore, immunofluorescence studies identify the subcellular relocalization of urokinase plasminogen activator receptor (uPAR), LIM and SH3 protein (LASP1), and vasodilatorstimulated protein (VASP) as a possible mechanism accounting for the loss of morphological polarity observed upon PDEF expression.

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“…The present study utilized the PC-3 human prostate cancer cell line as an experimental model. PC-3 cells are negative for EMT (18)(19)(20)(21) and positive for c-Met expression (22). The present study investigated the effects of HGF on the EMT and invasive potential of PC-3 cells.…”

Section: Introductionmentioning

confidence: 98%

Hepatocyte growth factor increases the invasive potential of PC-3 human prostate cancer cells via an ERK/MAPK and Zeb-1 signaling pathway

et al. 2015

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Abstract. Hepatocyte growth factor (HGF) has been implicated in epithelial-mesenchymal transition (EMT) in numerous types of cancer. However, to the best of our knowledge, there has been no previous evidence that HGF has a role in prostate cancer. The present study aimed to investigate the effect of HGF on EMT and invasive potential, as well as the underlying molecular mechanisms, in a human prostate cancer cell line. Therefore, PC-3 cells were treated with various concentrations of HGF for varying durations. EMT-associated proteins, including E-cadherin and vimentin, were examined by western blot analysis. The effects of HGF on cell proliferation, migration, invasion and tumorigenicity were assessed using MTT, wound-healing, Transwell and soft-agar assays. Subsequently, the role of c-Met in the mediation of EMT-like changes was investigated using reverse transcription-polymerase chain reaction, western blot analysis and gene knockdown by small interfering RNA. Finally, western blot analysis was used to quantify the expression of a downstream transcription factor and extracellular signal-related kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway proteins. The results indicated that treatment with HGF induced EMT-like changes and enhanced the invasive potential of PC-3 cells. There was an increase in the expression of ERK, phosphorylated-ERK and zinc finger E-box binding homeobox-1 (Zeb-1), suggesting that EMT-like changes may be mediated through the ERK/MAPK and Zeb-1 signaling pathway. Furthermore, HGF-mediated EMT-like changes were associated with c-Met activation, and these changes were able to be blocked by c-Met knockdown. The present study demonstrated that HGF-induced EMT increased the invasive potential of PC-3 human prostate cancer cells through activating the ERK/MAPK and Zeb-1 signaling pathway.

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Reduced PDEF Expression Increases Invasion and Expression of Mesenchymal Genes in Prostate Cancer Cells

Cited by 89 publications

References 37 publications

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Hepatocyte growth factor increases the invasive potential of PC-3 human prostate cancer cells via an ERK/MAPK and Zeb-1 signaling pathway

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