Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells

Li, Qiong; Wu, Mingfu; Wang, Hui; Xu, Gang; Zhu, Tao; Zhang, Yongtao; Liu, Ping; Song, Anping; Chen, Gang; Han, Zhiqiang; Zhou, Jianfeng; Li, Meng; Lu, Ye; Wang, Shixuan; Ma, Ding

doi:10.1016/j.canlet.2007.11.018

Cited by 74 publications

(65 citation statements)

References 31 publications

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“…Ezrin has been touted as a potentially therapeutic target in the metastasis of solid tumours (Li et al, 2008;Wu et al, 2011), and small molecule inhibitors of Ezrin have already been screened and shown to be effective in combating invasive osteosarcoma by impairing Ezrin phosphorylation and actininteractions (Bulut et al, 2012). Studies such as ours and that of Zhou et al (2010) show that the therapeutic applications of such inhibitors need not be limited to the metastases of solid tumours.…”

Section: Discussionmentioning

confidence: 94%

FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration

Corcoran

Cotter

2012

Free Radical Research

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Access to the full text of the published version may require a subscription. and ideas for this work, and who supported and believed in me throughout -I am grateful to have had the opportunity to learn from the best. I must also give a huge thank you to Kate Cotter, who made me feel at home from day one, and who has continued to be a tireless source of energy and assistance. RightsI was fortunate to interact with a vibrant, dynamic group in the Cotter Lab and I owe a huge thanks to every single member, past-Claire, Ruth, Carolyn, Chris, Ashley, To all the friends that I have made in U.C.C. and beyond during this process, as well as those friends lucky enough not to be involved but who still got to listen to all that whingeing-thank you! Lastly, I am most indebted to those closest to me. My mam -who is always ready to listen, comfort and reassure, and as a result probably knows more than she ever wanted to about cells and reactive oxygen species! My dad, a real scientist, who never stops teaching and never stops learning, and is still the person I turn to with my "homework" questions! I am so grateful to you both for your wisdom, encouragement and patience; truly I could not have achieved this without you. ToSinead and Dara, for all the much needed distractions and laughs, and for even being interested! And to John, for being there throughout, for the joy and the inspiration. To everyone still waiting for good news or the right medicine 'Happy is he who gets to know the reasons for things.' -Virgil DeclarationThis thesis has not been submitted in whole or in part to this or any other university for any degree and is, unless otherwise stated, the original work of the author. pathway may allow for combination therapies to be used to impede the emergence of resistance. However, the intracellular signal transduction pathway of FLT3 is relatively obscure. The objective of this study is to further elucidate this pathway, with particular focus on the redox signalling element which is thought to be involved. Signalling via reactive oxygen species is becoming increasingly recognised as a crucial aspect of physiological and pathological processes within the cell. The first part of this study examined the effects of NADPH oxidase-derived reactive oxygen species on the tyrosine phosphorylation levels of acute myeloid leukaemia cell lines. Using two-dimensional phosphotyrosine immunoblotting, a range of proteins were identified as undergoing tyrosine phosphorylation in response to iii NADPH oxidase activity. Ezrin, a cytoskeletal regulatory protein and substrate of Src kinase, was selected for further study.The next part of this study established that NADPH oxidase is subject to regulation by FLT3. Both wild type and oncogenic FLT3 signalling were shown to affect the expression of a key NADPH oxidase subunit, p22phox, and FLT3 was also demonstrated to drive intracellular reactive oxygen species production. The NADPH oxidase target protein, Ezrin, undergoes phosphorylation on two tyrosine residues downstream of FLT3 signalli...

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Section: Discussionmentioning

confidence: 94%

FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration

Corcoran

Cotter

2012

Free Radical Research

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“…The different distributions of ezrin and moesin were also reported during T cell activation [25,26]. [33][34][35][36]. Ezrin implication in cancer has been related to its interactions with a plethora of molecules related to metastatic functions.…”

Section: General Overview Of Erm Proteins (Ezrin Radixin Moesin)mentioning

confidence: 89%

“…Ezrin overexpression increased migration of metastatic melanoma [30], pancreatic cancer cells [31], or hepatocellular carcinoma [32]. Conversely, ezrin silencing or inhibition contributed to decreased cell motility [33][34][35][36]. Ezrin implication in cancer has been related to its interactions with a plethora of molecules related to metastatic functions.…”

Section: Erms In Pathological Processesmentioning

confidence: 99%

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

2013

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Ezrin, radixin and moesin (ERM) proteins are now more and more recognized to play a key role in a large number of important physiological processes such as morphogenesis, cancer metastasis and virus infection. Several recent reviews extensively discuss their biological functions [1][2][3][4]. In this review, we will first remind the main features of this family of proteins, which are now known as linkers and regulators of the plasma membrane/cytoskeleton linkage. We will then briefly review their implication in pathological processes such as cancer and viral infection. In a second part, we will focus on biochemical and biophysical approaches to study ERM interaction with lipid membranes and conformational change in well-defined environments. In vitro studies using biomimetic lipid membranes, especially large unilamellar vesicles (LUVs), giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) and recombinant proteins help to understand the molecular mechanism of conformational activation of ERM proteins. These tools are aimed to decorticate the different steps of the interaction, to simplify the experiments performed in vivo in much more complex biological environments. KeywordsEzrin; radixin and moesin; biomimetic membranes; phosphoinositol (4,5)-bisphosphate (PIP 2 ); large unilamellar vesicles; supported lipid bilayers; giant unilamelar vesicles Corresponding author: Catherine Picart, CNRS UMR 5628 (LMGP), Grenoble Institute of Technology and CNRS, 3 parvis Louis Néel, F-38016 Grenoble Cedex, France. Europe PMC Funders GroupAuthor Manuscript Biochimie. Author manuscript; available in PMC 2014 July 28. Published in final edited form as:Biochimie. 2013 January ; 95(1): 3-11. doi:10.1016/j.biochi.2012.09.033. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts Biological importance of Ezrin, Radixin and Moesin General overview of ERM proteins (Ezrin, Radixin, Moesin)ERM proteins are localized at the plasma membrane in actin-rich surface structures (Fig 1) [5], such as microvilli, membrane ruffles, and lamellipodia in gut cells, lymphocytes, hepatocytes, spermatozoids, fibroblasts and in a variety of other cell types [5][6][7][8][9]. They are involved in various physiological processes including establishment of cell polarity, cell motility and cell signaling [10]. They act as linkers between the plasma membrane and the cortical actin cytoskeleton. From a structural point of view, ERMs are constituted of 3 domains : a membrane binding domain, also known as FERM (for band 4.1 protein, ezrin, radixin and moesin), and intermediary region and a actin binding domain called C-ERMAD (for C-terminal ERM-association domain) (Fig 2A).The FERM domain, constituted of ~300 amino acids, is characteristic of the proteins of the band 4.1 superfamily. These proteins also present other types of domains, including PDZ, tyrosine phosphatase, SH2-like, tyrosine kinase, kinase-like, myosin head, and PH domains [11]. In ERM proteins, the FERM domain is followed by a long α-helical region, whi...

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“…Of the ERM family proteins, ezrin has been reported in many studies to be related to cancer progression and metastasis, thereby conferring poor prognosis (34)(35)(36)(37)(38)(39)(40)(41)(42)(43). In contrast, studies reporting that moesin has a direct effect on tumor incidence or progression are relatively few in number.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals overexpression of moesin and cytokeratin 17 proteins in colorectal carcinoma

Kim

Jung²,

Lee³

et al. 2011

Oncol Rep

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Abstract. The study of tumor biomarkers was gradually facilitated by the adoption of proteomic strategies due to less invasiveness and higher sensitivity. Colorectal cancer is one of the most commonly occurring cancers worldwide and its incidence has markedly increased in Korea. While the adoption of proteomic strategies facilitated the study of tumor biomarkers, to date, no common agreement has been derived from proteomic investigations regarding tumor markers of colorectal cancer. This study was designed to find molecules differentially expressed in colorectal cancer compared to non-tumor mucosa. Four colorectal adenocarcinoma and corresponding non-tumor tissue samples were analyzed to find previously unknown proteins via two-dimensional electrophoresis and MALDI-TOF/MS spectrometry. Western blot assays and tissue microarray (TMA) immunohistochemistry were performed to validate the identified proteins. Among the twelve up-regulated and one down-regulated proteins identified, moesin, cytokeratin (KRT) 17 and carbonic anhydrase I were validated by Western blot analysis and/or immunohistochemistry. On immunohistochemistry, both moesin and KRT17 demonstrated a tendency of increased expression as pT stage advanced. Both moesin and KRT17 were not expressed in normal colorectal epithelium. These two proteins may play a role in cancer invasion and/or metastasis in colorectal carcinoma, and could be candidate biomarkers for the diagnosis and prognosis of colorectal cancer.

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Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells

Cited by 74 publications

References 31 publications

FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration

FLT3-driven redox-modulation of Ezrin regulates leukaemic cell migration

Model membranes to shed light on the biochemical and physical properties of ezrin/radixin/moesin

Proteomic analysis reveals overexpression of moesin and cytokeratin 17 proteins in colorectal carcinoma

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