Decreased expression and prognostic role of EHD2 in human breast carcinoma: correlation with E-cadherin

Abstract

Decreased expression of epithelial cadherin (E-cadherin) has been noted to associate with aggressiveness and metastasis of breast cancer. The aim of this study was to examine the effect of C-Terminal EH domain-containing protein 2 (EHD2) expression on E-cadherin and related mechanism in the metastasis of breast cancer. Immunohistochemical analysis was performed in 96 human breast carcinoma samples and the data were correlated with clinicopathologic characteristics. Furthermore, Western blot analysis was performed for EHD2 and E-cadherin in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. We found that the expression of EHD2 was positively related with E-cadherin expression (P < 0.01), moreover, EHD2 expression was significantly correlated with histologic grade (P < 0.01). Meanwhile, E-cadherin expression obtained similar results. Kaplan-Meier survival analysis showed that decreased expression of EHD2 and E-cadherin exhibited a significant correlation with poor prognosis in human breast cancer (P < 0.01). While in vitro, we employed siRNA technique to knock down EHD2 expressions and observed their effects on breast cancer cells growth. EHD2 depletion by siRNA promoted PCNA expression, and it was concurrent with the decreased expression of epithelial marker E-cadherin and the increased expression of N-cadherin by Western blot analysis. Consistent with these observations, the suppression of EHD2 in breast cancer cells remarkably promoted cellular proliferation and migration. On the basis of these results, we suggested that EHD2 can inhibit the metastasis of human breast cancer by regulating the EMT key markers E-cadherin and N-cadherin.

Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors

“…4A ), indicating that the RCN1/PIGX/RCN2 complex would regulate the expression of these genes. Among these genes, ZIC1 and EHD2 were recently suggested to have a function related to human tumorigenesis ( 25 – 30 ). The upregulation of these potential downstream genes was validated with qRT-PCR ( Fig.…”

TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis

“…Abundant research has identified various tumor-derived secreted factors, including S100A8, S100A9, VEGF and Angpt2, important in premetastatic microenvironment formation in different tumor models (Shi et al 2015). Calprotectin S100A8 and S100A9 have been reported in association with tumor progression and metastasis, and these two proteins also possess a pivotal influence on chronic inflammation (Lukanidin and Sleeman 2012).…”

Cross-Species Proteomics Identifies CAPG and SBP1 as Crucial Invasiveness Biomarkers in Rat and Human Malignant Mesothelioma

“…The level of the first protein, which belongs to the EHD family associated with plasma membrane, has been reported to be reduced in human esophageal squamous carcinoma in comparison with adjacent normal tissues, linked to increased motility of the tumor cells [ 49 ]. Subsequently, a decreased expression was also observed, correlated with histological grade, in an immunohistochemical study of 96 human breast carcinoma samples, leading Shi et al to suggest that this protein inhibits metastasis by regulating EMT [ 50 ]. The second protein, which belongs to the small GTPase family Rab and to the Rab5 subfamily, presents an estrogen receptor-responsive element in its promoter region which can be dysregulated in breast cancer cells, the consequences of this key finding in cancer research having been reviewed by Chua and Tang [ 51 ].…”