ERM proteins in cancer progression

Abstract

Members of the ezrin–radixin–moesin (ERM) family of proteins are involved in multiple aspects of cell migration by acting both as crosslinkers between the membrane, receptors and the actin cytoskeleton, and as regulators of signalling molecules that are implicated in cell adhesion, cell polarity and migration. Increasing evidence suggests that the regulation of cell signalling and the cytoskeleton by ERM proteins is crucial during cancer progression. Thus, both their expression levels and subcellular localisation would affect tumour progression. High expression of ERM proteins has been shown in a variety of cancers. Mislocalisation of ERM proteins reduces the ability of cells to form cell–cell contacts and, therefore, promotes an invasive phenotype. Similarly, mislocalisation of ERM proteins impairs the formation of receptor complexes and alters the transmission of signals in response to growth factors, thereby facilitating tumour progression. In this Commentary, we address the structure, function and regulation of ERM proteins under normal physiological conditions as well as in cancer progression, with particular emphasis on cancers of epithelial origin, such as those from breast, lung and prostate. We also discuss any recent developments that have added to the understanding of the underlying molecular mechanisms and signalling pathways these proteins are involved in during cancer progression.

Moesin regulates the motility of oral cancer cells via MT1-MMP and E-cadherin/p120-catenin adhesion complex

“…The ERM family is composed of the proteins Ezrin, Moesin and Radixin which are thought to be a cross-linker between plasma membranes and actin-based cytoskeleton and subsequently participate in regulation of cell motility [16]. In the present study, Moesin expression was found decreased in the membrane and increased in the cytoplasm during the malignant transformation of oral epithelia, and cytoplasmic overexpression of Moesin correlated with nodal metastasis and poor prognosis of OSCCs, which was consistent with previous studies [17,18].…”

Identification of a novel stress regulated FERM domain containing cytosolic protein having PTP activity in Setaria cervi, a bovine filarial parasite

“…It is well known that protein tyrosine phosphatases possessing an ERM domain belong to FERM (band four-point-one, ezrin, radixin, moesin homology) domain family known as PTPL1/PTP-BAS protein. This band 4.1/FERM domain consists of an actin binding, peptide binding and phosphatidyl inositol phosphate binding motif [14]. Four out of the above 16 peptides showed significant similarity to the putative B. malayi PTPL protein.…”

“…in). It has been reported that FERM domains when bound to PtsdIns (4,5)P2 at plasma membrane are phosphorylated by specific kinases leading to unfolding of the F-actin domain, thereby exposing it to link with the varied cytoskeletal and transmembrane proteins such as Rho GTPases, Wnt-bcatenin, cadherin and Akt kinases [14]. Thus, the presence of FERM domain containing proteins is often associated with the presence of different transmembrane and cytoskeletal proteins like actin.…”

Plasticity of tumor cell migration: acquisition of new properties or return to the past?

“…These proteins both directly provide the link between actin cortex and plasma membrane through their ability to interact with trans membrane proteins and the underlying cytoskeleton and also can regulate the activities of signal transduction pathways responsible for cell polarity and migration [146]. It was shown that moesin participates in formation of membrane underlying actin cortex in non polarized rounded lymphocytes and is accumulated in their tail region during migration (lymphocytes move using amoe boid motion) [147].…”