J Korean Soc Menopause.  2012 Aug;18(2):81-93.

Ezrin is an Essential Marker for Metastasis of Gynecologic Cancer

• Choi SD

Abstract

Ezrin, a membrane cytoskeleton linking protein, is a member of ezrin/radixin/moesin (ERM) that regulates cell shape, motility and cell to cell interaction via linking the contractile elements of the cell to transmembrane proteins. Ezrin, through this mechanism, has been thought to play an important role in cancer progression and distant metastasis. In addition, high levels of ezrin expression have been noted in many cancers, such as breast, colon, osteosarcoma, and prostate cancer. Gynecologic cancer cells, with high levels of ezrin expression, have more invasive potential than that of the lower levels of ezrin expressed cancer cells. High levels of ezrin expression are also related to the advanced histological grade and poor outcome. Recently, several reports have also demonstrated that ezrin expression is enhanced and almost localized at the membranous portion in high stage tumor cells and metastatic gynecologic cancer cells. Therefore, in the near future, ezrin levels and its cellular location might serve as essential markers for the metastasis of gynecologic cancers.

Keyword

Ezrin; Genital neoplasms female; Metastasis

MeSH Terms

Breast
Cell Communication
Cell Shape
Colon
Cytoskeletal Proteins
Cytoskeleton
Membranes
Neoplasm Metastasis
Osteosarcoma
Prostatic Neoplasms
Proteins
Cytoskeletal Proteins
Proteins

Figure

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  Fig. 1 The hypothesis of ezrin's role in the process of metastasis.

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  Fig. 2 Schematic view of ezrin activation and deactivation.

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  Fig. 3 A Possible model for activation and function of ezrin. (A) The dormant form of Ezrin with the N-terminal ezrin/radixin/moesin (ERM) associated domain (N-ERMAD) associated with C-ERMAD in cytoplasm. It is transformed into the active form after phosphorylation of specific sites. The N-terminal of activated ezrin can directly bind to C-terminal of transmembrane proteins, and C-ERMAD of ezrin can bind to filamentous actin (F-actin). Ezrin can also act as a linker protein between specific membranous proteins and F-actin via ERM-binding phosphoprotein 50 (EBP50). (B) Activated ezrin can displace guanosine diphosphate (GDP) dissociation inhibitor (GDI) from the Rho-GDI complex, which can stimulate PI4P5 kinase activity. GDP/GTP exchange factor (GEF) catalyzes this reaction. (C) Phosphatidylinositol phosphate (PIP) is changed to phosphatidylinosito (4, 5)-bisphosphate (PIP2) by PI4P5 Kinase. Sequentially PIP2 can change dormant ezrin into its active form. [Modified from "ERM proteins and merlin: integrators at the cell cortex", by Bretscher A, Edwards K and Fehon RG, 2002, Nat Rev Mol Cell Biol, 3, p. 586-99. Copyright 2012 by the RightLink®. Modified with permission]. C: carboxy terminal, N: amino terminal, N-ERMAD: amino-ERM associated domain, C-ERMAD: carboxy-ERM association domain, F-actin: filamentous actin, EBP50: ERM-binding phosphoprotein 50, GDI: guanine nucleotide dissociation inhibitor, PI4P5 Kinase: phosphatidylinositol-4-phosphate 5-kinase, NHE-1, 3: sodium-hydrogen exchanger 1, 3, PDGF-R: platelet derived growth factor receptor, CD44: hyaluronic acid receptor, CD43: leucosialin, ICAM-1, 2: intercellular adhesion molecule-1, 2.

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  Fig. 4 A model for ezrin activation and the Rho pathway.

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