Ezrin promotes breast cancer progression by modulating AKT signals

Abstract

BACKGROUND: Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear. METHODS: Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression. RESULTS: In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC. CONCLUSIONS: In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

Bioactive Ent-Kaurane Diterpenes Oridonin and Irudonin Prevent Cancer Cells Migration by Interacting with the Actin Cytoskeleton Controller Ezrin

“…Previous studies reported that Ezrin promotes migration, invasion and cancer progression in vitro and in vivo , by interacting with AKT thereby regulating the AKT pathway in breast cancer [ 14 ]. Thus, we investigated whether the ability of Ori and Iru to bind Ezrin in A375 and MKN28, may affect AKT signalling pathways.…”

“…Moreover, since Ezrin has been shown to modulate Matrix Metalloproteinases activity in cancer cells [ 9 , 14 , 24 ], we examined the effect of the two diterpenes on either MMP-9 or MMP-2 activity. To that aim we carried out gel zymography assay on cell-conditioned media from A375 and MKN28 cells, revealing ( Figure 6 A) in both cell lines that treatment with 10 μM of each compound was able to significantly reduce MMP-9 and MMP-2 gelatinolytic activity.…”

“…Cancer cells colony formation by Ezrin was reported [ 14 , 25 ]. Therefore, we assayed the reproductive rate of cancer cells following treatments with 10 μM Ori or Iru.…”

“…This is a key event occurring during development, cell migration and cancer progression, which is associated with the reorganization of the actin cytoskeleton. Indeed, during EMT, cells reorganize their actin cytoskeleton and this event enables dynamic cell elongation and directional motility, thus increasing the migratory phenotype [ 12 , 13 , 14 ]. Other data indicate that Ori might accomplish its inhibitory effect by interfering with cytoskeleton dynamics and function.…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…Cancer-related functions of PCBP2, TIA-1, HuR/ELAVL1, SERBP1, YTHDC2, YTHDF2 (Mapofthecell database) were described above. All experimentally defined partners of eEF1Bγ picked up by Cytoscape to build molecular networks, are linked to cancer as well [2,[125][126][127][128][129][130][131][132].…”