Ezrin Promotes Ovarian Carcinoma Cell Invasion and Its Retained Expression Predicts Poor Prognosis in Ovarian Carcinoma

Köbel, Martin; Gradhand, Elise; Zeng, Katharina; Schmitt, Wolfgang; Kriese, Karen; Lantzsch, Tilmann; Wolters, Matthias; Dittmer, Jürgen; Strauß, Hans; Thomssen, Christoph; Hauptmann, Steffen

doi:10.1097/01.pgp.0000185410.39050.ac

Cited by 61 publications

(43 citation statements)

References 17 publications

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“…Some studies showed that high expression of Ezrin might be correlated with the invasion of different tumours. [18][19][20][21][22] However, some investigators suggested that Ezrin gene might be a tumour suppressor, inhibiting tumour development. Others proposed that the location of Ezrin protein in cells migrated with the occurrence and development of tumour, but the total amount of Ezrin protein showed no change.…”

Section: Discussionmentioning

confidence: 99%

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Shen

Shen²,

Zheng³

et al. 2009

CIM

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Clin Invest Med 2009; 32 (2): E180-E188. AbstractPurpose: To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. Methods: Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonary metastasis and overall survival time were carried out based on the clinical data. Results: mRNA levels of Ezrin and Six1 genes in osteosarcoma tissues were higher than those in adjacent normal tissues (P=0.015, 0.025). The mRNA levels of Ezrin, CD44 and Six1 genes were closely correlated with Enneking GTM clinical staging, while no correlations were demonstrated between the mRNA level of these genes with sex, age, location or pathological types. In addition, we demonstrated that the high mRNA level of Ezrin gene was related to shorter lung metastasis-free and overall survival time of the Chinese patients with osteosarcoma (P<0.001). Conclusion: Our data suggest that Ezrin, but not CD44 and Six1, could be a prognostic factor and a predictor of potential lung metastasis in osteosarcoma. Further large sample studies need to be done to confirm the potential value of Ezrin as a new therapeutic target.Osteosarcoma is the most common malignant primary bone tumour with high capacity of distant metastasis.Lungs and bones are the common sites for metastases. About 20% of patients present visible metastases with imaging at diagnosis and about 25% patients have metastases during the course of treatment. 1 Once the metastases, especially pulmonary metastases, occur it is difficult to treat them due to their poor prognosis. Currently, the characteristics of high metastasis in osteosarcoma cell lines remain unclear. Therefore, it is necessary to discover new indicators to assess the metastasis and prognosis in clinic.Recent studies have shown that ERM protein family members (Ezrin, Radixin and Moesin) play vital roles in the occurrence and progression of tumours. They can regulate cell activities in adhesion, migration and penetration and act as the link of cell membranes to cytoskeleton. 2-4 CD44, a cell adhesion molecule, was shown to play an important role in the process of invasion and metastasis of tumour cells, while the investigators found that Ezrin might have a synergistic effect with CD44 on the progression of tumours. 3 Thus, the prognosis of sub-group with CD44 and Ezrin high expression should be analyzed and discussed. Homology domain transcription factor Six1, a material needed in the development of normal cells is often abnormal in the process of tumour occur-CLINCAL REPORT

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Section: Discussionmentioning

confidence: 99%

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Shen

Shen²,

Zheng³

et al. 2009

CIM

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“…All histologic slides were re-evaluated by two pathologists (E. Gradhand and S. Hauptmann) using a multihead microscope. Tumor patients and tissue samples were, in part, described elsewhere (28). Histology was classified according to the WHO, and grading was assessed according to Silverberg (29).…”

Section: Methodsmentioning

confidence: 99%

Both Germ Line and Somatic Genetics of the p53 Pathway Affect Ovarian Cancer Incidence and Survival

Bartel¹,

Jung²,

Böhnke³

et al. 2008

Clinical Cancer Research

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Purpose: Although p53 is one of the most studied genes/proteins in ovarian carcinomas, the predictive value of p53 alterations is still ambiguous. Experimental Design: We performed analyses of the TP53 mutational status and its protein expression using immunohistochemistry. Moreover, the single nucleotide polymorphism SNP309 in the P2 promoter of the MDM2 gene was investigated.We correlated the results with age of onset and outcome from 107 patients with ovarian carcinoma. Results: In our study, we identified a large group of patients with p53 overexpression despite having a wild-type gene (49% of all patients with wild-type TP53). This was associated with a significantly shortened overall survival time (P = 0.019). Patients with p53 alterations (especially those with overexpression of wild-type TP53) were also more refractory to chemotherapy compared with patients with normal p53 (P = 0.027).The G-allele of SNP309 is associated with an earlier age of onset in patients with estrogen receptor^overexpressing FIGO stage III disease (P = 0.048). In contrast, in patients with FIGO stage III disease, a weakened p53 pathway (either the G-allele of SNP309 or a TP53 mutation) was correlated with increased overall survival compared with patients whose tumors were wild-type for bothTP53 and SNP309 (P = 0.0035). Conclusion: Our study provides evidence that both germ line and somatic alterations of the p53 pathway influence the incidence and survival of ovarian carcinoma, and it underscores the importance of assessing the functionality of p53 in order to predict the sensitivity of platinumbased chemotherapies and patient outcome.

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“…and S.H.). Tumor patients and tissue samples were in part described elsewhere (6,20). Additional 49 samples from ovarian carcinoma patients were provided by the Tumor Bank Ovarian Cancer (TOC), Department of Gynecology and Obstetrics of the Charit e (Berlin, Germany).…”

Section: Patient Population and Clinical Datamentioning

confidence: 99%

An Illegitimate microRNA Target Site within the 3′ UTR of MDM4 Affects Ovarian Cancer Progression and Chemosensitivity

et al. 2010

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Overexpression of MDM4 (also known as MDMX or HDMX) is thought to promote tumorigenesis by decreasing p53 tumor suppressor function. Even modest decrease in Mdm4 levels affects tumorigenesis in mice, suggesting that genetic variants of MDM4 might have similar effects in humans. We sequenced the MDM4 gene in a series of ovarian cancer cell lines and carcinomas to identify mutations and/or single nucleotide polymorphisms (SNPs). We identified an SNP (SNP34091) in the 3 0 -UTR of MDM4 that creates a putative target site for hsa-miR-191, a microRNA that is highly expressed in normal and tumor tissues. Biochemical evidence supports specific miR-191-dependent regulation of the MDM4-C, but not MDM4-A, variant. Consistently, the A-allele was associated with statistically significant increased expression of MDM4 mRNA and protein levels in ovarian carcinomas. Importantly, the wild-type genotype (A/A) is more frequent (57.8% vs. 42.2% for A/C and C/C, respectively) in patients with high-grade carcinomas than in patients with low-grade carcinomas (47.2% vs. 52.5% for A/A and A/C þ C/C, respectively). Moreover, A/A patients who do not express the estrogen receptor had a 4.2-fold [95% confidence interval (CI) ¼ 1.2-13.5; P ¼ 0.02] increased risk of recurrence and 5.5-fold (95% CI ¼ 1.5-20.5; P ¼ 0.01) increased risk of tumor-related death. Unexpectedly, the frequency of p53 mutations was not significantly lower in A/A patients. We conclude that acquisition of an illegitimate miR-191 target site causes downregulation of MDM4 expression, thereby significantly delaying ovarian carcinoma progression and tumor-related death. Importantly, these effects appear to be, at least partly, independent of p53. Cancer Res; 70(23); 9641-9. Ó2010 AACR.

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Ezrin Promotes Ovarian Carcinoma Cell Invasion and Its Retained Expression Predicts Poor Prognosis in Ovarian Carcinoma

Cited by 61 publications

References 17 publications

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Expression of Ezrin correlates with lung metastasis in Chinese patients with osteosarcoma

Both Germ Line and Somatic Genetics of the p53 Pathway Affect Ovarian Cancer Incidence and Survival

An Illegitimate microRNA Target Site within the 3′ UTR of MDM4 Affects Ovarian Cancer Progression and Chemosensitivity

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