Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas

Köbel, Martin; Langhammer, T.; Hüttelmaier, Stefan; Schmitt, Wolfgang; Kriese, Karen; Dittmer, Jürgen; Strauß, Hans‐Georg; Thomssen, Christoph; Hauptmann, Steffen

doi:10.1038/modpathol.3800567

Cited by 55 publications

(46 citation statements)

References 18 publications

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“…Ezrin is often aberrantly expressed in human cancers and thus may be a potentially new prognostic marker and/or therapeutic target for some carcinomas (12,18,19). In this study, we also found that ezrin overexpression in ESCCs was associated with poor survival.…”

Section: Discussionsupporting

confidence: 68%

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Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Gao

Cui

et al. 2009

Journal of Biological Chemistry

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Ezrin, encoded by VIL2, is a membrane-cytoskeletal linker protein that has been suggested to be involved in tumorigenesis. Ezrin expression in esophageal squamous cell carcinoma (ESCC) was described recently, but its clinical significance and the molecular mechanism underlying its regulated expression remain unclear. Thus, we retrospectively evaluated ezrin expression by immunohistochemistry in a tissue microarray representing 193 ESCCs. Ezrin overexpression in 90 of 193 tumors (46.6%) was associated with poor survival (p ‫؍‬ 0.048). We then explored the mechanism by which ezrin expression is controlled in ESCC by assessing the transcriptional regulatory regions of human VIL2 by fusing deletions or site-directed mutants of the 5-flanking region of the gene to a luciferase reporter. We found that the region ؊87/؊32 containing consensus Sp1 (؊75/؊69) and AP-1 (؊64/؊58) binding sites is crucial for VIL2 promoter activity in esophageal carcinoma cells

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Section: Discussionsupporting

confidence: 68%

“…Moreover, both in vivo and in vitro experiments suggest that ezrin may affect tumor formation and tumor invasiveness directly (17). These findings of ezrin up-regulation associated with epithelial tumor metastasis and invasion make ezrin a potentially new prognostic marker and/or therapeutic target for some carcinomas (12,18,19).…”

mentioning

confidence: 99%

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Gao

Cui

et al. 2009

Journal of Biological Chemistry

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“…In addition we showed that the abnormal localization of ezrin in the cytoplasm of HNSCC cells correlates with poor overall survival [15]. While the mechanism for cytoplasmic localization is unknown and whether cytoplasmic ezrin contributes to aggressive phenotype or is merely a biomarker for it, there is mounting evidence that expression of ezrin in several types of tumors correlates with poor outcome [16][17][18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

“…We have shown previously that a high level of cytoplasmic ezrin correlates or that high levels of cytoplasmic ezrin correlate with poor survival in head and neck squamous cell carcinoma [15], and recent studies show that increased expression of ezrin is also associated with poor clinical outcome in a variety of human cancers [16][17][18][19][20][21].…”

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confidence: 99%

Cytoplasmic Ezrin and Moesin Correlate with Poor Survival in Head and Neck Squamous Cell Carcinoma

Brandwein-Gensler

Smith

Kawachi

et al. 2012

Head and Neck Pathol

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Members of the 4.1 superfamily of proteins, including ezrin, moesin, merlin, and willin regulate many normal physiologic processes such as cellular shape, motility, and proliferation. In addition, they contribute both to tumor development and tumor progression. We reported previously that strong cytoplasmic ezrin expression was independently associated with poorer patient survival. One hundred and thirty-one histologically confirmed primary head and neck squamous cell carcinomas were examined prospectively for cancer progression and survival at a large health care center in the Bronx, NY, USA. Immunohistochemical analysis of ezrin, moesin, merlin, and willin expression in tissue microarray samples of primary head and neck squamous cell carcinoma revealed a significant association of increased cytoplasmic ezrin with poor cancer survival. Global RNA analyses suggest that cancers with high cytoplasmic ezrin have a more invasive phenotype.This study supports our previous findings associating cytoplasmic ezrin with more aggressive behavior and poorer outcome and indicates the need for a multi-institutional study to validate the use of cytoplasmic ezrin as a biomarker for treatment planning in head and neck squamous cell carcinoma.

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“…Upregulation of ezrin correlates with invasive characteristics of malignant cell lines, as well as with malignancy, metastatic behavior and poor clinical outcome of diverse cancers (Geiger et al, 2000;Makitie et al, 2001;Ohtani et al, 2002;Ilmonen et al, 2005;Weng et al, 2005;Kobel et al, 2006;Bruce et al, 2007;Elzagheid et al, 2008). By a microarray approach, Khanna et al (2004) identified ezrin as an essential protein for experimental metastatic osteosarcoma and a marker of poor outcome in spontaneous canine osteosarcomas and in pediatric osteosarcomas.…”

Section: Introductionmentioning

confidence: 99%

Ezrin is key regulator of Src-induced malignant phenotype in three-dimensional environment

et al. 2011

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The oncogenic tyrosine kinase Src has a role in cancer development, especially by promoting invasive and metastatic behavior. It is, however, unclear which of the Srcregulated signaling cascades induce malignant phenotype in three-dimensional environment. One of Src substrates is ezrin, a cytoskeletal organiser and regulator of signal transduction. Ezrin expression correlates with poor outcome of diverse cancers and is essential in experimental metastatic osteosarcoma. We reconstituted genetically ezrin-deficient cells with wild-type (WT) or phosphorylation-deficient Y477F ezrin together with constitutively active Src. In two-dimensional cultures, Src induced malignant features regardless of the presence or absence of ezrin. In contrast, only WT ezrin-expressing cells grew efficiently in soft agar or in suspension. In Matrigel, only WT ezrin significantly promoted growth and invasion, and was targeted to specific regions on the plasma membrane. WT and Y477F ezrin-expressing cells showed marked differences only when growing or scattering in threedimensional matrix. Additional experiments showed that Y477-phosphorylated ezrin is also needed for the growth of Src-transformed epithelial cells in three-dimensional matrix. Cells lacking functional ezrin had reduced cyclin D levels and fewer cells in G2 þ S phase, possibly as a consequence of abnormal mTOR signaling, as ezrin Y477F cells showed lower expression of phosphorylated intermediates downstream of mTOR than WT cells. We conclude that the pathways activated by Src depend on the type of environment and that ezrin is a crucial element of Src-induced malignant features in cells growing inside three-dimensional environment.

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Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas

Cited by 55 publications

References 18 publications

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Cytoplasmic Ezrin and Moesin Correlate with Poor Survival in Head and Neck Squamous Cell Carcinoma

Ezrin is key regulator of Src-induced malignant phenotype in three-dimensional environment

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