NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma

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• 作者：Maria-Magdalena Georgescu (1) (2)
  Paul Yell (1)
  Bret C Mobley (3)
  Ping Shang (1)
  Theodora Georgescu (2)
  Shih-Hsiu J Wang (4)
  Peter Canoll (4)
  Kimmo J Hatanpaa (1)
  Charles L White III (1)
  Jack M Raisanen (1)
  
  1. Department of Pathology ; The University of Texas Southwestern Medical Center ; Dallas ; TX ; 75390 ; USA
  2. Department of Neuro-Oncology ; The University of Texas MD Anderson Cancer Center ; Houston ; TX ; 77030 ; USA
  3. Department of Pathology ; Vanderbilt University Medical Center ; Nashville ; TN ; 37232 ; USA
  4. Department of Pathology ; Columbia University ; New York ; NY ; 10032 ; USA
  
• 关键词：NHERF1/EBP50 ; Ependymoma ; Hydrocephalus ; Polarity ; Moesin ; PTEN
• 刊名：Acta Neuropathologica Communications
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：3
• 期：1
• 全文大小：1,919 KB
• 参考文献：1. Bigio, MR (2010) Ependymal cells: biology and pathology. Acta Neuropathol 119: pp. 55-73 CrossRef
  2. Spassky, N, Merkle, FT, Flames, N, Tramontin, AD, Garcia-Verdugo, JM, Alvarez-Buylla, A (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25: pp. 10-18 CrossRef
  3. Lee, L (2013) Riding the wave of ependymal cilia: genetic susceptibility to hydrocephalus in primary ciliary dyskinesia. J Neurosci Res 91: pp. 1117-1132 CrossRef
  4. Kilday, JP, Rahman, R, Dyer, S (2009) Pediatric ependymoma: biological perspectives. Mol Cancer Res 7: pp. 765-786 CrossRef
  5. Iqbal, MS, Lewis, J (2013) An overview of the management of adult ependymomas with emphasis on relapsed disease. Clin Oncol 25: pp. 726-733 CrossRef
  6. Stemmer-Rachamimov, AO, Wiederhold, T, Nielsen, GP (2001) NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas. Am J Pathol 158: pp. 57-62 CrossRef
  7. Ardura, JA, Friedman, PA (2011) Regulation of G protein-coupled receptor function by Na+/H+ exchange regulatory factors. Pharmacol Rev 63: pp. 882-900 CrossRef
  8. Georgescu, MM, Morales, FC, Molina, JR, Hayashi, Y (2008) Roles of NHERF1/EBP50 in cancer. Curr Mol Med 8: pp. 459-468 CrossRef
  9. Hayashi, Y, Molina, JR, Hamilton, SR, Georgescu, MM (2010) NHERF1/EBP50 is a new marker in colorectal cancer. Neoplasia 12: pp. 1013-1022
  10. Kreimann, EL, Morales, FC, Orbeta-Cruz, J (2007) Cortical stabilization of beta-catenin contributes to NHERF1/EBP50 tumor suppressor function. Oncogene 26: pp. 5290-5299 CrossRef
  11. Takahashi, Y, Morales, FC, Kreimann, EL, Georgescu, MM (2006) PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J 25: pp. 910-920 CrossRef
  12. Georgescu, MM, Cote, G, Agarwal, NK, White, CL (2014) NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane. Neoplasia 16: pp. 365-374 CrossRef
  13. Mangia, A, Chiriatti, A, Bellizzi, A (2009) Biological role of NHERF1 protein expression in breast cancer. Histopathology 55: pp. 600-608 CrossRef
  14. Molina, JR, Morales, FC, Hayashi, Y, Aldape, KD, Georgescu, MM (2010) Loss of PTEN binding adapter protein NHERF1 from plasma membrane in glioblastoma contributes to PTEN inactivation. Cancer Res 70: pp. 6697-6703 CrossRef
  15. Kamiya, K, Michel, V, Giraudet, F (2014) An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells. Proc Natl Acad Sci U S A 111: pp. 9307-9312 CrossRef
  16. Morales, FC, Takahashi, Y, Kreimann, EL, Georgescu, MM (2004) Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia. Proc Natl Acad Sci U S A 101: pp. 17705-17710 CrossRef
  17. Malafronte, PJ, LePage, EM, Hatanpaa, KJ, Burns, DK, White, CL, Raisanen, J (2014) Expression of MAP 2 by haemangioblastomas: an immunohistochemical study with implications for diagnosis. Pathology 46: pp. 450-451 CrossRef
  18. Morales, FC, Hayashi, Y, Pelt, CS, Georgescu, MM (2012) NHERF1/EBP50 controls lactation by establishing basal membrane polarity complexes with prolactin receptor. Cell Death Dis 3: pp. e391 CrossRef
  19. Shenolikar, S, Voltz, JW, Minkoff, CM, Wade, JB, Weinman, EJ (2002) Targeted disruption of the mouse NHERF-1 gene promotes internalization of proximal tubule sodium-phosphate cotransporter type IIa and renal phosphate wasting. Proc Natl Acad Sci U S A 99: pp. 11470-11475 CrossRef
  20. Aziz, AA, Coleman, L, Morokoff, A, Maixner, W (2005) Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in children?. Pediatr Radiol 35: pp. 815-818 CrossRef
  21. Hasselblatt, M, Paulus, W (2003) Sensitivity and specificity of epithelial membrane antigen staining patterns in ependymomas. Acta Neuropathol 106: pp. 385-388 CrossRef
  22. Lazar, CS, Cresson, CM, Lauffenburger, DA, Gill, GN (2004) The Na+/H+ exchanger regulatory factor stabilizes epidermal growth factor receptors at the cell surface. Mol Biol Cell 15: pp. 5470-5480 CrossRef
  23. Maudsley, S, Zamah, AM, Rahman, N (2000) Platelet-derived growth factor receptor association with Na(+)/H(+) exchanger regulatory factor potentiates receptor activity. Mol Cell Biol 20: pp. 8352-8363 CrossRef
  24. Mohler, PJ, Kreda, SM, Boucher, RC, Sudol, M, Stutts, MJ, Milgram, SL (1999) Yes-associated protein 65 localizes p62(c-Yes) to the apical compartment of airway epithelia by association with EBP50. J Cell Biol 147: pp. 879-890 CrossRef
  25. Molina, JR, Agarwal, NK, Morales, FC (2012) PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. Oncogene 31: pp. 1264-1274 CrossRef
  26. Reczek, D, Berryman, M, Bretscher, A (1997) Identification of EBP50: A PDZ-containing phosphoprotein that associates with members of the ezrin-radixin-moesin family. J Cell Biol 139: pp. 169-179 CrossRef
  27. Shibata, T, Chuma, M, Kokubu, A, Sakamoto, M, Hirohashi, S (2003) EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma. Hepatology 38: pp. 178-186 CrossRef
  28. Ebert, C, Haken, M, Meyer-Puttlitz, B (1999) Molecular genetic analysis of ependymal tumors. NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas. Am J Pathol 155: pp. 627-632 CrossRef
  29. Martin-Belmonte, F, Gassama, A, Datta, A (2007) PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128: pp. 383-397 CrossRef
  30. Taylor, MD, Poppleton, H, Fuller, C (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8: pp. 323-335 CrossRef
  31. Witt, H, Mack, SC, Ryzhova, M (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20: pp. 143-157 CrossRef
  32. Lee, JE, Gleeson, JG (2011) Cilia in the nervous system: linking cilia function and neurodevelopmental disorders. Curr Opin Neurol 24: pp. 98-105 CrossRef
  33. Yuan, S, Sun, Z (2013) Expanding horizons: ciliary proteins reach beyond cilia. Annu Rev Genet 47: pp. 353-376 CrossRef
  34. Mullin JM (2004) Epithelial barriers, compartmentation, and cancer. Sci STKE (216):pe2
  35. Lin, YY, Hsu, YH, Huang, HY (2012) Aberrant nuclear localization of EBP50 promotes colorectal carcinogenesis in xenotransplanted mice by modulating TCF-1 and beta-catenin interactions. J Clin Invest 122: pp. 1881-1894 CrossRef
  36. Saponaro, C, Malfettone, A, Dell鈥橢ndice, TS (2014) The prognostic value of the Na(+)/ H(+) exchanger regulatory factor 1 (NHERF1) protein in cancer. Cancer Biomark 14: pp. 177-184
  
• 刊物主题：Neurosciences;
• 出版者：BioMed Central
• ISSN：2051-5960

文摘

NHERF1/EBP50, an adaptor protein required for epithelial morphogenesis, has been implicated in the progression of various human malignancies. NHERF1-deficient mice have intestinal brush border structural defects and we report here that they also have disorganized ependymal cilia with development of non-obstructive hydrocephalus. Examination of mouse and human brain tissues revealed highest NHERF1 expression at the apical plasma membrane of ependymal cells. In ependymal tumors, NHERF1 expression was retained in polarized membrane structures, such as microlumens, rosettes and canals, where it co-localized with some of its ligands, such as moesin and PTEN. Analysis of a comprehensive panel of 113 tumors showed robust NHERF1 labeling of microlumens in 100% of ependymomas, subependymomas, and pediatric anaplastic ependymomas, and in 67% of adult anaplastic ependymomas. NHERF1 staining was present in 35% of ependymoma cases that lacked reactivity for EMA, the routine immunohistochemical marker used for ependymoma diagnosis. NHERF1 labeling of microlumens was either absent or rarely seen in other types of brain tumors analyzed, denoting NHERF1 as a reliable diagnostic marker of ependymal tumors. Anaplastic foci and a subset of adult anaplastic ependymomas showed complete absence of NHERF1-labeled polarity structures, consistent with a loss of differentiation in these aggressive tumors. These data highlight a role for NHERF1 in ependymal morphogenesis with direct application to the diagnosis of ependymal tumors.