Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas

Sarrió, David; Moreno‐Bueno, Gema; Sánchez-Estévez, Carolina; Bañón-Rodríguez, Inmaculada; Hernandez-Cortes, Gines; Hardisson, David; Palacios, José

doi:10.1016/j.humpath.2006.03.003

Cited by 69 publications

(59 citation statements)

References 36 publications

(74 reference statements)

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“…Furthermore, eIF6 is known to interact with integrin-b4. 36 Deregulation of the WNT signalling is well described in ovarian serous adenocarcinoma pathogenesis, [37][38][39][40] indicating that eIF6 may have multiple biological roles in ovarian serous adenocarcinoma tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

et al. 2008

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy.

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Section: Discussionmentioning

confidence: 99%

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

et al. 2008

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“…N-cadherin has been detected in benign and borderline tumors [51] as well as malignant effusions [52]. Moderate N-cadherin staining of serous and endometroid tumors has been reported, with mucinous and clear cell tumors demonstrating low or undetectable expression [18,[53][54][55]. To date, no relationship between N-cadherin positivity and tumor stage or metastasis has been established [53].…”

Section: B Cadherin Expression In Eocmentioning

confidence: 99%

“…Although control of E-cadherin expression in EOC has not been studied extensively, examples of mechanisms detected in other tumor types have been identified. Somatic mutations in the E-cadherin gene are rare in ovarian carcinomas [56], but activating mutations of β-catenin are detected in one histologic subtype of ovarian carcinoma, ovarian endometrioid adenocarcinoma [5,55,67,68]. Methylation of the E-cadherin promoter has been detected in epithelial ovarian neoplasms and associated with reduced E-cadherin protein [69][70][71].…”

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confidence: 99%

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Hudson

Zeineldin

Stack

2008

Clin Exp Metastasis

165

172

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The mesodermally derived normal ovarian surface epithelium (OSE) displays both epithelial and mesenchymal characteristics and exhibits remarkable phenotypic plasticity during post-ovulatory repair. The majority of epithelial ovarian carcinomas (EOC) are derived from the OSE and represent the most lethal of all gynecological malignancies, as most patients (~70%) present at diagnosis with disseminated intra-abdominal metastasis. The predominant pattern of EOC metastasis involves pelvic dissemination rather than lymphatic or hematologic spread, distinguishing EOC from other solid tumors. Acquisition of the metastatic phenotype involves a complex series of interrelated cellular events leading to dissociation (shedding) and dispersal of malignant cells. A key event in this process is disruption of cell-cell contacts via modulation of intercellular junctional components. In contrast to most carcinomas that downregulate E-cadherin expression during tumor progression, an unique feature of primary well-differentiated ovarian cancers is a gain of epithelial features, characterized by an increase in expression of E-cadherin. Subsequent reacquisition of mesenchymal features is observed in more advanced tumors with concomitant loss of E-cadherin expression and/ or function during progression to metastasis. The functional consequences of this remarkable phenotypic plasticity are not fully understood, but may play a role in modulation of cell survival in suspension (ascites), chemoresistance, and intraperitoneal anchoring of metastatic lesions. Keywords ovarian cancer; epithelium; cadherin; keratin; vimentin; epithelial-mesenchymal transition; plasticity Ovarian Cancer-OverviewTumors arising from the ovarian epithelium account for ~90% of ovarian malignancies and epithelial ovarian carcinoma (EOC) is the leading cause of death from gynecologic malignancy, resulting in approximately 15,280 deaths in the United States alone in 2006 [1]. These distressing statistics are largely due to the low detection rate of disease confined to the ovary (stage 1) when 5-year survival is >90%. Approximately 75% of women are initially diagnosed with disseminated intra-abdominal disease (stage III-IV) and have a 5-year survival of <20%.Ovarian tumors are pathologically heterogeneous with four major histotypes: serous, endometroid, clear cell and mucinous. These classifications are histogenetically based on The early steps of EOC metastasis involve shedding of the cells from the primary tumor to form free floating cells or multi-cellular aggregates (MCAs) in ascites [ Fig. 1]. Cell-cell and cell-matrix adhesion molecules mediate interaction of metastasizing tumor cells with mesothelial cells lining the inner surface of the peritoneal cavity and the sub-mesothelial extracellular matrix (ECM). Localized proteolytic degradation of sub-mesothelial ECM components facilitates migration of tumor cells and anchoring of secondary lesions on adjacent pelvic organs, and at later stages, metastasis to distant organs [9,10]. However, the majority of wo...

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“…Aberrant redistribution of p120 has been observed in several epithelial malignancies, including gastric cancer (Jawhari et al, 1999;Karatzas et al, 1999;Karayiannakis et al, 1999;Thoreson and Reynolds, 2002;Mayerle et al, 2003). Typically found at low levels in the nuclei of normal cells, increased levels of p120 have been observed in nuclei of tumor cells (Mayerle et al, 2003;Wijnhoven et al, 2005;Sarrio et al, 2006), and recent evidence has revealed that nuclear p120 acts to relieve transcriptional repression mediated by Kaiso, a member of the broad complex, tramtrak, bric a brac/pox virus, and zinc finger family (BTB/POZ) (Daniel and Reynolds, 1999). The Kaiso/p120 complex can modulate noncanonical Wnt signaling (Kim et al, 2004), and, along with T cell factor (TCF)/ ␤-catenin complexes, coordinately regulate canonical Wnt gene targets such as cyclin D1 and mmp-7 (Park et al, 2005;Spring et al, 2005), both of which are up-regulated by H. pylori (Hirata et al, 2001;Bebb et al, 2003;Crawford et al, 2003;Wroblewski et al, 2003;Chang et al, 2006).…”

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confidence: 99%

p120 and Kaiso RegulateHelicobacter pylori-induced Expression of Matrix Metalloproteinase-7

Ogden

Wroblewski

Weydig

et al. 2008

MBoC

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Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Matrix metalloproteinase (MMP)-7, a member of a family of enzymes with tumor-initiating properties, is overexpressed in premalignant and malignant gastric lesions, and H. pylori cag ؉ strains selectively increase MMP-7 protein levels in gastric epithelial cells in vitro and in vivo. We now report that H. pylori-mediated mmp-7 induction is transcriptionally regulated via aberrant activation of p120-catenin (p120), a component of adherens junctions. H. pylori increases mmp-7 mRNA levels in a cagand p120-dependent manner and induces translocation of p120 to the nucleus in vitro and in a novel ex vivo gastric gland culture system. Nuclear translocation of p120 in response to H. pylori relieves Kaiso-mediated transcriptional repression of mmp-7, which is implicated in tumorigenesis. These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag ؉ isolates may explain in part the augmentation in gastric cancer risk associated with these strains. INTRODUCTIONHelicobacter pylori induces an inflammatory response in the stomach that persists for decades, and biological costs incurred by this pathogen include an increased risk for gastric adenocarcinoma and non-Hodgkins lymphoma of the stomach (Nomura et al., 1991;Parsonnet et al., 1991;Peterson, 1991;Hansson et al., 1993;Correa, 1996;Uemura et al., 2001;Peek and Blaser, 2002;Moss and Sood, 2003). However, only a fraction of colonized persons ever develop neoplasia, and enhanced cancer risk is related to strain-specific differences, aberrant host responses, and/or specific interactions between microbial and host determinants.H. pylori strains that possess the cytotoxin-associated gene (cag) pathogenicity island increase the risk for cancer compared with strains that lack this genetic locus (Peek and Blaser, 2002). The cag island encodes proteins, such as CagE, that form a type IV secretion system that translocates components of bacterial peptidoglycan and CagA, the product of the terminal gene of the island, into host cells (Asahi et al., 2000;Backert et al., 2000;Odenbreit et al., 2000;Stein et al., 2000;Selbach et al., 2002;Viala et al., 2004). After translocation, peptidoglycan initiates innate immune signaling via activation of the intracellular pattern recognition receptor, Nod-1, and the transcriptional activator nuclear factor-B (NF-B) (Viala et al., 2004). Intracellular CagA undergoes Src-dependent tyrosine phosphorylation and activates a eukaryotic phosphatase, leading to dephosphorylation of host cell proteins and cellular morphological changes (Backert et al., 2000;Higashi et al., 2002;Selbach et al., 2002;Stein et al., 2002). Recently, CagA has been shown to activate ␤-catenin and...

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Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas

Cited by 69 publications

References 36 publications

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

p120 and Kaiso RegulateHelicobacter pylori-induced Expression of Matrix Metalloproteinase-7

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