GASTROINTESTNAL CANCERS
Jian-Jun Xie(1) / 2011 / Oesophageal squamous cell cancer / Intense Cytoplasmic expression (n=307) associated with poor survival (p=0.023, Kaplan Meier), especially stage III/IV (p=0.0002) but not stage I/II, with multi-variate cox proportional hazard model revealing ezrin to be an independent prognostic factor (p=0.011) / none
Jian-Jun Xie(2) / 2009 / Oesophageal squamous cell cancer / Correlation of expression of Ezrin with CTGF, CYR61 and ATF3 in 80 cancer and 50 normal oesophageal samples / Ezrin knockdown in cell lines and cDNA micro-array reveal differential expression of 297 genes including ATF3, CTGF and CYR61 along with pathway analysis revealing alteration in TGFβ and MAPK pathways
Hongmei Zeng(3) / 2006 / Oesophageal squamous cell cancer / Ezrin mRNA was 3.6 times more prevalent in normal mucosa as compared to cancer and PCNA expression was higher in ezrin down regulated group.
L Yang (4) / 2012 / Gall Baldder / Increased expression of Ezrin, HGF or c-met was an independent bad-prognostic predictor in gallbladder adenocarcinoma.
Jingchun Jin (5) / 2012 / Gastric Cancer / Strong expression of Ezrin was significantly correlated with poor prognosis of gastric cancer
WW Zheng (6) / 2012 / Gastric Cancer / miR-183 is down-regulated in stage II( GC, and associated with the differentiation, metastasis, and prognosis / Ezrin is a potential regulatory protein of miR-183.
Jing Zhao(7) / 2011 / gastric cancer / Ezrin and cMEt expression were tumour specific biomarkers
Li Li(8) / 2011 / gastric cancer / Ezrin overexpression was significantly associated with lymph node and distant metastasis and poor survival (except stage IV patients) in 436 patients
Li-Lin Fan(9) / 2011 / gastric cancer / H Pylori induced cell migration, adhesion and alteration of morphology was dependent on Ezrin (AGS cell line)
Nebil Bal(10) / 2007 / gastric cancer / H pylori associated overexpression of ezrin influencing survival (n=75; 53 intestinal and 22 diffuse type)
Yong Chen(11) / 2011 / hepatocellular cancer / Phosphorylation of Thr 567 was associated with tumour thrombi (mass spectrometric) / Thr 567 phosphorylation was mediated by Rhokinase inducing membrane ruffling
Yun Kyung Kang(12) / 2010 / hepatocellular cancer / Ezrin expression associated with poor overall and disease-free survival in multivariate analysis (hazard ratio 1.905, p=0.011; n=100 resected specimen)
Chun-Nan Yeh(13) / 2009 / hepatocellular cancer / HBV-HCC patients undergoing hepatectomy (n=104) had association of ezrin overexpression with smaller tumour size, cirrhotic background, poor differentiation and vascular invasion / WT Ezrin transfection into HEP3B cells resulted in de-differentiation and increased invasion
Daiki Okamura(14) / 2008 / hepatocellular cancer / Ezrin expression associated with early recurrence in multivariate analysis (n=77 resected specimen) and with CK19 but not CK7 expression
ZQ Zhong (15) / 2012 / Pancreatic Cancer / RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1
YX Meng (16) / 2012 / Pancreatic Cancer / Ezrin expression affects the cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion in pancreatic cancer cell line Panc-1
Steven Hustinx(17) / 2005 / periampullary neoplasms / Heterogeneous group of neoplasms studied which included 300 primary pancreatic cancers, 54 ampullary cancers and 33 non invasive IPMN which demonstrated association with poor differentiation of expression of ERM proteins and 14-3-3 sigma proteins
Shinichi Aishima(18) / 2011 / cholangiocarcinoma / S100P (p=0.001) and ezrin (p=0.0728) expression associated with poor survival in peripheral type of resected cholangiocarcinoma , with increased expression from pre-malignant to malignant lesions
Ponlapat Yonglitthipagon (19) / 2012 / Cholangiocarcinoma / Altered expression of peroxiredoxin 1 and Radixin-Moesin-binding phosphoprotein 50 may be used as prognostic markers in cholangiocarcinoma
A Ben-Shmuel (20) / 2012 / Colon cancer / L1-mediated signaling by the L1-Ezrin-NF-κB pathway, that induces IGFBP-2 expression, has an important role in CRC progression
Nancy Gavert(21) / 2010 / colon cancer / Cell-neural adhesion molecule (L1CAM) binds to ezrin and mediates phosphorylation of IkappaB to promote metastasis
Yazhou Cui(22) / 2009 / pancreatic cancer / Radixin, moesin but not ezrin had significant overexpression in patients with LN metastasis as identified by MALDI TOF and confirmed by WB and IHC
Hemant Kocher(23) / 2009 / pancreatic cancer / Ezrin overexpression correlation with tumour progression and disease free survival (log-rank test, p=0.019) / Ezrin interacts with cortactin to form podosomal rosettes which digest underlying substrate to promote metastasis
Ta-Sen Yeh(24) / 2005 / pancreatic cystic neoplasms / solid pseudo papillary tumour (SPT) (n = 12), mutinous cystic neoplasm (MCN) (n = 18), intraductal papillary mucinous tumor (IPMT) (n = 18), and ductal adenocarcinoma (PA) (n = 73) demonstrated the membranous expression was associated with poor survival (p=0.02) / Sodium Butyrate led to decreased membranous expression in PANC1 cells
Eija Korkeila (25) / 2012 / Rectal Cancer / Negative/weak Ezrin expression in preoperative biopsies was associated with 47.5-fold risk of death from this disease
Fredrik Jörgren (26) / 2012 / Rectal Cancer / Increased expression of Ezrin may represent a marker of aggressive biological behaviour in rectal cancer
Eija Korkeila(27) / 2011 / rectal cancer / In univariate analysis negative ezrin expression in pre-operative biopsy resulted in longer disease-free and disease-specific survival which was lost in multivariate analysis of 176 rectal cancers studied. / Ezrin expression was not influenced by radiation
Adam Elzagheid(28) / 2008 / colorectal cancer / Univariate analysis demonstrated poor survival (p=0.035) and 5-year metastasis (p=0.018) but lost predictive power in multivariate analysis.
D Nowak(29) / 2010 / colon cancer / Four colon cancer cell lines and sublines demonstrated an increased peripheral localisation of ezrin associated with increased phosphorylation of cofilin in more motile cell sublines
Amelie Rebillard(30) / 2010 / colon cancer / Cisplatinum induced apoptosis is mediated by Fas receptor resulting in ROCk and subsequent ezrin phosphorylation
WG Jiang(31) / 1996 / colon cancer / EGF and IL11 enhanced while IL2, IL8, IL10 and IGF1 inhibited ezrin expression
Yu-Ching Wei(32) / 2009 / GIST / In multivariate analysis, ezrin (p=0.008, risk ratio 3.581) along with Ki67 labelling index, high risk category, non gastric origin, remained unique predictors of poor survival in 347 cases studied.
OTHER CANCERS
Neetha Parameswaran (33) / 2013 / B-Cell Lymphoma / Novel role for Ezrin as a spatial adaptor that couples JNK signaling components to the BCR signalosome, thus facilitating JNK activation
Qing Chen(34) / 2011 / breast cancer / VCAM1 along with Ezrin protects cells from apoptosis during metastasis
Shuhui Zheng(35) / 2011 / breast cancer / Oestrogen promotes cellular movement through activation of Ezrin
SM Potter(36) / 2011 / breast cancer / Ezrin expression was increased in the cytoplasm due to paracrine stimulation from stromal cells
Simona Donatello(37) / 2012 / Breast cancer / New model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration
Alan Arslan (38) / 2012 / Breast Cancer / The cytoplasmic relocalization of Ezrin may therefore represent a novel marker for large malignant tumour size, reflecting the unique biology of LABC
Qingchang Li (39) / 2012 / Lung Cancer / Ezrin expression correlated significantly with lymphatic metastasis and advanced TNM stage
Ho Won Lee (40) / 2012 / Non small cell lung cancer / Ezrin might be a molecular marker to predict poor prognosis of NSCLC
QY Chen (41) / 2012 / Non small cell lung cancer / Combined detection of Ezrin, E-cadherin and CD44V6 expression is helpful in evaluating the metastasis and prognosis of non-small cell lung cancer
QX Zhang(42) / 2011 / Non small cell lung cancer / In 89 patients, ezrin expression(40 patients) was asscoiated with increased tumour stage, lymph node metastasism overall and disease free survival. In 73 frozen tissues, phospho-ezrin expression was higher in cancer.
Benjamin Bruce(43) / 2007 / 5000 breast, lung, prostate cancer and sarcomas / Most association in breast cancers (p=0.025) and sarcomas (p=0.02) with poor outcome and advancing grade respectively
Minjing Zou(44) / 2004 / thyroid / S1004 along with c-met, ezrin, cadherin and integrin-motility related protein1 differentially upregulated in metastatic cell sub-line (ARO-met2) as compared to parental cell line (ARO), confirmed in 49 tumour specimens with RTPCR
Martin Kobel(45) / 2006 / ovarian cancer / Ezrin is an independent risk factor for poor prognosis in multivariate analysis (p=0.012, relative risk 2.39) in 105 patients assessed of which 49% had positive ezrin expression / Invasion mediated by Ezrin but not moesin in SKOV3 cells
Eung-Kyun Kim(46) / 2011 / ovarian cancer / Lysophosphatidic acid induced cell migration is mediated by RhoA and ERM proteins
Martin Kobel(47) / 2006 / endometroid cancer / Ezrin is an independent risk factor for poor prognosis in multivariate analysis (p=0.047, relative risk 2.2) in 164 patients assessed
XiFu Shang (48) / 2012 / Osteosarcoma / SiRNAs targeting Ezrin may have therapeutic potential as inhibitors of osteosarcoma metastasis
Hye-Rim Park(49) / 2006 / osteosarcoma / Ezrin expression assocaited with high grade osteosarcoma
L Ren(50) / 2011 / osteosarcoma / Ezrin phosphorylation at Thr567 results in altered cellular metabolism promoting metastatic phenotype
L Heiska(51) / 2011 / osteosarcoma / in 3D environment, Src induced malignant behaviour (motility) is conferred by Ezrin (Y477F, phosphorylation deficient mutant)
X Wan(52) / 2009 / osteosarcoma / Ezrin cooperated with b4 integrin to promote metastatic behaviour
L Ren(53) / 2009 / osteosarcoma / Protein Kinase C mediated phosphorylation of ezrin at the invasive front in human and murine osteosarcoma
Yanlin Yu(54) / 2004 / rhabdomyosarcoma / Ezrin and Six1 are critical regulators of metastatic behaviour
Ana Carneiro (55) / 2011 / soft tissue sarcoma / Ezrin expression predicts local recurrence (HR 2,4, p=0.02) and metastasis (HR1.8, p=0.07) in 256 sarcomas studied
References
1. Xie JJ, Xu LY, Wu ZY, Zhao Q, Xu XE, Wu JY, Huang Q, Li EM. Prognostic implication of ezrin expression in esophageal squamous cell carcinoma. J Surg Oncol. 2011 Oct;104(5):538-43. PubMed PMID: 21416469. Epub 2011/03/19. eng.
2. Xie JJ, Xu LY, Xie YM, Zhang HH, Cai WJ, Zhou F, Shen ZY, Li EM. Roles of ezrin in the growth and invasiveness of esophageal squamous carcinoma cells. Int J Cancer. 2009 Jun 1;124(11):2549-58. PubMed PMID: 19165868. Epub 2009/01/24. eng.
3. Zeng H, Xu L, Xiao D, Zhang H, Wu X, Zheng R, Li Q, Niu Y, Shen Z, Li E. Altered expression of ezrin in esophageal squamous cell carcinoma. J Histochem Cytochem. 2006 Aug;54(8):889-96. PubMed PMID: 16585385.
4. Yang L, Guo T, Jiang S, Yang Z. Expression of ezrin, HGF and c-met and its clinicopathological significance in the benign and malignant lesions of the gallbladder. Hepatogastroenterology. 2012;59(118):1769-75. doi: 10.5754/hge11744.
5. Jin J, Jin T, Quan M, Piao Y, Lin Z. Ezrin overexpression predicts the poor prognosis of gastric adenocarcinoma. Diagn Pathol. 2012;7:135.(doi):10.1186/746-596-7-135.
6. Zheng WW, Huang CM, Xie JW, Zheng CH, Li P, Wang JB, Lin JX. [Expression of microRNA-183 in stage II ( gastric cancer and its association with Ezrin protein]. Zhonghua Wei Chang Wai Ke Za Zhi. 2012;15(7):723-6.
7. Zhao J, Zhang X, Xin Y. Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas. Histol Histopathol. 2011 Sep;26(9):1111-20. PubMed PMID: 21751142. Epub 2011/07/14. eng.
8. Li L, Wang YY, Zhao ZS, Ma J. Ezrin is associated with gastric cancer progression and prognosis. Pathol Oncol Res. 2011 Dec;17(4):909-15. PubMed PMID: 21717114. Epub 2011/07/01. eng.
9. Fan LL, Chen DF, Lan CH, Liu KY, Fang DC. Knockdown of ezrin via RNA interference suppresses Helicobacter pylori-enhanced invasion of gastric cancer cells. Cancer Biol Ther. 2011 Apr 15;11(8):746-52. PubMed PMID: 21282970. Epub 2011/02/02. eng.
10. Bal N, Yildirim S, Nursal TZ, Bolat F, Kayaselcuk F. Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type. World J Gastroenterol. 2007 Jul 21;13(27):3726-9. PubMed PMID: 17659733. Epub 2007/07/31. eng.
11. Chen Y, Wang D, Guo Z, Zhao J, Wu B, Deng H, Zhou T, Xiang H, Gao F, Yu X, Liao J, Ward T, Xia P, Emenari C, Ding X, Thompson W, Ma K, Zhu J, Aikhionbare F, Dou K, Cheng SY, Yao X. Rho kinase phosphorylation promotes ezrin-mediated metastasis in hepatocellular carcinoma. Cancer Res. 2011 Mar 1;71(5):1721-9. PubMed PMID: 21363921. Epub 2011/03/03. eng.
12. Kang YK, Hong SW, Lee H, Kim WH. Prognostic implications of ezrin expression in human hepatocellular carcinoma. Mol Carcinog. 2011 Sep;49(9):798-804. PubMed PMID: 20572160. Epub 2010/06/24. eng.
13. Yeh CN, Pang ST, Chen TW, Wu RC, Weng WH, Chen MF. Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma. BMC Cancer. 2009;9:233. PubMed PMID: 19604375. Epub 2009/07/17. eng.
14. Okamura D, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Miyazaki M. Ezrin expression is associated with hepatocellular carcinoma possibly derived from progenitor cells and early recurrence after surgical resection. Mod Pathol. 2008 Jul;21(7):847-55. PubMed PMID: 18425081. Epub 2008/04/22. eng.
15. Zhong ZQ, Song MM, He Y, Cheng S, Yuan HS. Knockdown of Ezrin by RNA interference reverses malignant behavior of human pancreatic cancer cells in vitro. Asian Pac J Cancer Prev. 2012;13(8):3781-9.
16. Meng YX, Yu SN, Lu ZH, Chen J. [Effects of ezrin silencing on pancreatic cancer cell line Panc-1]. Zhonghua Bing Li Xue Za Zhi. 2012;41(12):833-6.
17. Hustinx SR, Fukushima N, Zahurak ML, Riall TS, Maitra A, Brosens L, Cameron JL, Yeo CJ, Offerhaus GJ, Hruban RH, Goggins M. Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms. Cancer Biol Ther. 2005 May;4(5):596-601. PubMed PMID: 15908786.
18. Aishima S, Fujita N, Mano Y, Kubo Y, Tanaka Y, Taketomi A, Shirabe K, Maehara Y, Oda Y. Different roles of S100P overexpression in intrahepatic cholangiocarcinoma: carcinogenesis of perihilar type and aggressive behavior of peripheral type. Am J Surg Pathol. 2011 Apr;35(4):590-8. PubMed PMID: 21412073. Epub 2011/03/18. eng.
19. Yonglitthipagon P, Pairojkul C, Chamgramol Y, Loukas A, Mulvenna J, Bethony J, Bhudhisawasdi V, Sripa B. Prognostic significance of peroxiredoxin 1 and ezrin-radixin-moesin–binding phosphoprotein 50 in cholangiocarcinoma. Human Pathology. 2012;43(10):1719-30.
20. Ben-Shmuel A, Shvab A, Gavert N, Brabletz T, Ben-Ze'ev A. Global analysis of L1-transcriptomes identified IGFBP-2 as a target of ezrin and NF-kappaB signaling that promotes colon cancer progression. SO - Oncogene 2012 Aug 6 doi: 101038/onc2012340.