• Sanjay Chauhan
  • Ryan Childers
  • Jennifer Himes
  • Andrea Pierce
  • Sabrina Sykes
  • Kelvin W. Pond
  • Susan Kunz
  • Roger L. Miesfeld
Part of the Cancer Metastasis – Biology and Treatment book series (CMBT, volume 9)


The FERM domain protein EHM2 (EPB41L4B) was first isolated and characterized based on its elevated expression in highly metastatic mouse melanoma cells. We recently found that human EHM2 is androgen-regulated in a cancer cell line model of steroid-induced cytoskeletal reorganization, and expression profiling analyses by others have shown that it is a primary steroidregulated gene in rat liver and human lung cells. Bioinformatic analysis of human EHM2 revealed that it is a member of a unique subfamily of FERM domain proteins that includes the Drosophila YURT gene. Analysis of YURT protein functions in Drosophila have shown that it is required for dorsal closure during embryogenesis and is involved in mediating epithelial cell migration. We have used immunostaining to analyze steroid-induced and ectopic expression of EHM2 in the human fibrosarcoma cell line HT-1080 and found that it is localized to the cell membrane and associated with cytoskeletal reorganization. We have also found that EHM2 is highly expressed in the metastatic prostate cancer cell lines LNCaP, DU-145 and PC-3 cells, and moreover, that EHM2 transcripts are present at significantly higher levels in human prostate tumors than in non-malignant prostate cells. Based on these data, we propose that elevated expression of EHM2 may enhance the metastatic properties of advanced prostate cancers.


Prostate Cancer Cell Line Guanine Nucleotide Exchange Factor Cytoskeletal Reorganization Ferm Domain Prostate Cancer Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gautreau, A., Louvard, D., Arpin, M. ERM proteins and NF2 tumor suppressor: the Yin and Yang of cortical actin organization and cell growth signaling. Curr Opin Cell Biol 2002,14(1): 104–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Ponta, H., Sherman, L., Herrlich, P.A. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003,4(1): 33–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Sun, C.X., Robb, V.A., Gutmann, D.H. Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J Cell Sci 2002, 115(Pt 21): 3991–4000.PubMedCrossRefGoogle Scholar
  4. 4.
    Hamada, K., Shimizu, T., Yonemura, S, Tsukita, S, Hakoshima, T. Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex. Embo J 2003,22(3): 502–14.PubMedCrossRefGoogle Scholar
  5. 5.
    Shimizu, T., Seto, A., Maita, N., Hamada, K., Tsukita, S., Hakoshima, T. Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J Biol Chem 2002,277(12): 10332–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Smith, W.J., Nassar, N., Bretscher, A., Cerione, R.A., Karplus, P.A. Structure of the Active N-terminal Domain of Ezrin. J Biol Chem 2003,278(7): 4949–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Chishti, A.H., Kim, A.C., Marfatia, S.M., et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci 1998,23(8): 281–2.PubMedCrossRefGoogle Scholar
  8. 8.
    Chauhan, S., Pandey, R., Way, J., et al. Androgen regulation of the human FERM domain encoding gene EHM2 in a cell model of steroid-induced differentiation. Biochem Biophys Res Commun 2003, 310: 421–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Kubo, T., Yamashita, T., Yamaguchi, A., Sumimoto, H., Hosokawa, K., Tohyama, M. A novel FERM domain including guanine nucleotide exchange factor is involved in Rac signaling and regulates neurite remodeling. J Neurosci 2002,2(19): 8504–13.Google Scholar
  10. 10.
    Yu, Y., Khan, J., Khanna, C., Helman, L., Meltzer, P.S., Merlino, G. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med 2004,10(2): 175–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Pang, S.T., Dillner, K., Wu, X., Pousette, A., Norstedt, G., Flores-Morales, A. Gene expression profiling of androgen deficiency predicts a pathway of prostate apoptosis that involves genes related to oxidative stress. Endocrinology 2002,143(12): 4897–906.PubMedCrossRefGoogle Scholar
  12. 12.
    Chauhan, S., Kunz, S., Davis, K., et al. Androgen control of cell proliferation and cytoskeletal reorganization in human fibrosarcoma cells: role of RhoB signaling. J Biol Chem 2004, 279(2): 937–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Hoover, K.B., Bryant, P.J. Drosophila Yurt is a new protein-4.1-like protein required for epithelial morphogenesis. Dev Genes Evol 2002,212(5): 230–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Liu, J.P., Jessell, T.M. A role for rhoB in the delamination of neural crest cells from the dorsal neural tube. Development 1998,125(24): 5055–67.PubMedGoogle Scholar
  15. 15.
    Li, P.X., Wong, J., Ayed, A., et al. Placental transforming growth factor-beta is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J Biol Chem 2000, 275(26): 20127–35.PubMedCrossRefGoogle Scholar
  16. 16.
    Razani B., Wang, X.B., Engelman, J.A., et al. Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Mol Cell Biol 2002, 22(7): 2329–44.PubMedCrossRefGoogle Scholar
  17. 17.
    Russell, D.L., Doyle, K.M., Gonzales-Robayna, I., Pipaon, C., Richards, J.S. Egr-1 induction in rat granulosa cells by follicle-stimulating hormone and luteinizing hormone: combinatorial regulation by transcription factors cyclic adenosine 3',5'-monophosphate regulatory element binding protein, serum response factor, spl, and early growth response factor-1. Mol Endocrinol 2003,17(4): 520–33.PubMedCrossRefGoogle Scholar
  18. 18.
    Raposo, G., Cordonnier, M.N., Tenza, D., et al. Association of myosin I alpha with endosomes and lysosomes in mammalian cells. Mol Biol Cell 1999, 10(5): 1477–94.PubMedGoogle Scholar
  19. 19.
    Shimizu, K., Nagamachi, Y., Tani, M., et al. Molecular cloning of a novel NF2/ERM/4.1 superfamily gene, ehm2, that is expressed in high-metastatic K1735 murine melanoma cells. Genomics 2000, 65(2): 113–20.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang, J.C., Derynck, M.K., Nonaka, D.F., Khodabakhsh, D.B., Haqq, C., Yamamoto, K.R. Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes. Proc Natl Acad Sci U S A 2004,101(44): 15603–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Phuc, Le P., Friedman, J.R., Schug, J., et al. Glucocorticoid Receptor-Dependent Gene Regulatory Networks. PLoS Genet 2005,1(2): e16.CrossRefGoogle Scholar
  22. 22.
    Rhodes, D.R., Yu, J., Shanker, K., et al. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci U S A 2004,101(25): 9309–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Rhodes, D.R., Yu, J., Shanker, K., et al. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia 2004, 6(1): 1–6.PubMedGoogle Scholar
  24. 24.
    Dhanasekaran, S.M., Barrette, T.R., Ghosh, D., et al. Delineation of prognostic biomarkers in prostate cancer. Nature 2001,412(6849): 822–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Luo, J.H., Yu, Y.P., Cieply, K., et al. Gene expression analysis of prostate cancers. Mol Carcinog 2002, 33(1): 25–35.PubMedCrossRefGoogle Scholar
  26. 26.
    Luo, J., Duggaa, D.J., Chen, Y., et al. Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Res 2001, 61(12): 4683–8.PubMedGoogle Scholar
  27. 27.
    Ramakers, C., Ruijter, J.M., Deprez, R.H., Moorman, A.F. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 2003, 339(1): 62–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Pfaffl, M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001,29(9): e45.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Sanjay Chauhan
    • 1
  • Ryan Childers
    • 1
  • Jennifer Himes
    • 1
  • Andrea Pierce
    • 1
  • Sabrina Sykes
    • 1
  • Kelvin W. Pond
    • 3
  • Susan Kunz
    • 1
  • Roger L. Miesfeld
    • 1
    • 2
  1. 1.Departments of Biochemistry and Molecular BiophysicsUSA
  2. 2.Molecular and Cellular BiologyUSA
  3. 3.Arizona Cancer CenterUniversity of ArizonaTucsonUSA

Personalised recommendations