4478

MSN

moesin;MSN;moesin

epididymis luminal protein 70|membrane-organizing extension spike protein

Xq11.1

protein-coding

BACKGROUND: The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. METHODS: In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. RESULTS: On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. CONCLUSIONS: These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

Three closely related proteins, ezrin, radixin, and moesin (ERM), which primarily act as a linker between the plasma membrane and the cytoskeleton, are involved in many cellular functions, including regulation of actin cytoskeleton, control of cell shape, adhesion and motility, and modulation of signaling pathways. Although, ezrin is now recognized as a key component in tumor metastasis, the functional role of the radixin and moesin in tumor metastasis has not been established. In the present study, we chose highly metastatic human gastric carcinoma SGC-7901 cells, which express all of the ERM proteins as a model to examine the functional roles of these proteins in tumor metastasis. Ezrin, radixin or moesin stable knockdown SGC-7901 cell lines were established using siRNA methodology. In vitro cell migration and invasion studies showed that either ezrin, radixin or moesin specific deficiency in the cells caused the substantial reduction of the cell migration and invasion. Western blotting and immunofluorescence analysis showed that the expression of E-cadherin was also significantly increased when any member of ERM proteins was downregulated. Our results indicated that these three ERM proteins play similar roles in the SGC-7901 cell metastatic potential and their roles of upregulating the expression of E-cadherin may be important in tumor progression.

PURPOSE: Moesin is a linking protein of the submembraneous cytoskeleton and plays a key role in the control of cell morphology, adhesion, and motility. The aim of the present study was to elucidate the clinical significance of expression patterns of moesin in patients with oral squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: Immunohistochemistry for moesin monoclonal antibody was performed on 103 paraffin-embedded specimens from patients with primary OSCC, including 30 patients with locoregional lymph node metastasis, and in the sections from nude mice transplanted with two cell lines derived from a single human tongue cancer (SQUU-A and SQUU-B). RESULTS: expression patterns of moesin in OSCCs were divided into three groups: membranous pattern; mixed pattern; and cytoplasmic pattern. These expression patterns correlated with tumor size, lymph node metastasis, mode of invasion, differentiation, and lymphocytic infiltration. In about two-thirds of the patients with metastatic lymph node, homogeneous cytoplasmic expression was detected in the metastatic lymph nodes. In addition, SQUU-B with high metastatic potential showed more reduced levels of membrane-bound moesin than SQUU-A with low metastatic potential. A multivariate analysis demonstrated that expression patterns of moesin can be an independent prognostic factor. CONCLUSIONS: Our results suggest that moesin expression contributed to discriminating between patients with the potentiality for locoregional lymph node metastasis and those with a better prognosis and might improve the definition of suitable therapy for each.

The aim of the study was to observe different protein profiles in pancreatic cancer with and without lymph node metastasis (LNM), and search for novel LNM-associated proteins, which would help to understand the metastatic mechanisms and provide targets for therapeutic interventions. cancer nests were manually miscrodissected from 8 LNM and 7 non-LNM pancreatic cancer tissues, and the protein extracts were then separated by difference gel electrophoresis (DIGE) and identified by MALDI-TOF-TOF. Four differently regulated proteins, ezrin, radixin, moesin, and c14orf166, were selected for further validation by Western blot and immunohistochemistry. In DIGE analysis, we identified 18 up-regulated proteins and 15 down-regulated proteins in LNM pancreatic cancer nests compared with non-LNM ones. Western blot and immunohistochemical analyses confirmed that radixin, moesin and c14orf166, but not ezrin, had significantly higher expression levels in LNM pancreatic cancers than in non-LNM controls. In conclusion, the specific protein profiles found in this study might provide new insights into the mechanism of lymph node metastasis. For the first time, c14orf166 was identified asa novel metastasis-associated protein, and the roles of radixin, moesin and c14orf166 in cancer metastasis deserve further investigations.

OBJECTIVE: To investigate the effects of Ezrin, Moesin and E-Cadherin on the invasion and metastasis of papillary thyroid carcinoma(PTC). METHODS: The 81 paraffin-embedded specimen of PTC treated in The Second Clinical College of Harbin Medical University from 2005 to 2008 were examined immunohistochemically for Ezrin, Moesin, and E-Cadherin. Normal thyroid tissues adjacent to cancer were control. The correlation of Ezrin, Moesin, and E-Cadherin expressions and clinical features of PTC, including gender, age, tumor size, invasion, lymph node metastasis, and TNM stage, was analyzed. RESULTS: Positive staining rates of Ezrin and Moesin in PTC were significantly higher than those in control (chi(2) were 61.691 and 57.949, P < 0.01, respectively). Positive staining rate of E-Cadherin in PTC was significantly lower than that in control (chi(2) = 64.241, P < 0.01). The positive expression rates of Ezrin and Moesin in PTC increased in the subgroups with age >/= 45 years, local invasion, lymph node metastasis and stage III-IV, with significant difference respectively (P < 0.01), while the positive expression rate of E-Cadherin in PTC significantly decreased (P < 0.01). CONCLUSIONS: The up-regulation expressions of Ezrin and Moesin and the down-regulation expression of E-Cadherin were associated with the invasion and metastasis of PTC. Combined detection of Ezrin, Moesin and E-Cadherin in PTC might served as an important predictor for the invasion, metastasis and prognosis of PTC.