Eps8 regulates cellular proliferation and migration of breast cancer

Abstract

The role of Eps8 in human breast cancer was studied, and we found that Eps8 was overexpressed in >60% of human breast cancer samples compared with adjacent normal breast tissues by immunohistochemical analysis. Eps8 was highly expressed in the highly invasive breast cancer cell line MDA-MB‑231 compared with the weakly invasive breast cancer cell lines MCF7 and MDA-MB‑468. MCF7 cell line stably expressing Eps8 was established by G418 screening, and the ectopic expression of Eps8 enhanced MCF7 breast cancer cell growth and survival as assessed by MTT analysis, cell viability and liquid colony formation, whereas the lentiviral expression of Eps8 shRNA in MDA-MB‑231 cells resulted in a significant reduction in cellular growth and proliferation in vitro and in vivo. Furthermore, Eps8 knockdown inhibited breast cancer cell migration in wound healing assays, decreased the number and size of EGF-induced filopodia and increased the sensitivity of breast cancer cells to cisplatin analyzed by MTT assays. Eps8 knockdown decreased the levels of phosphorylated extracellular signal-regulated protein kinase (ERK) and MMP9 but increased p53. Moreover, Eps8 knockdown suppressed a partial EMT-like transition and showed a significant increase in E-cadherin and decrease in N-cadherin and vimentin. These results suggest that Eps8 is overexpressed in human breast cancers, possibly by regulating ERK signaling, MMP9, p53 and EMT-like transition to affect breast cancer cell growth, migration and invasion. Therefore, Eps8 might represent a novel potential target in human breast cancer therapy.

PTK6 Localized at the Plasma Membrane Promotes Cell Proliferation and MigratiOn Through Phosphorylation of Eps8

“…It is known that Eps8‐mediated cell proliferation and migration accompany ERK activation [Maa et al, ; Chen et al, ], and FAK phosphorylation [Maa et al, ]. Therefore, we examined whether PTK6‐mediated Eps8 phosphorylation regulates activation of ERK and FAK.…”

“…Eps8 is upregulated in various tumors, including breast, cervical, colon, hematologic, oral, and pancreatic cancers [Li et al, ]. Eps8 overexpression induces tumorigenesis, proliferation, migration, and metastasis through EGFR‐activated signaling pathways [Maa et al, ; Welsch et al, ; Xu et al, ; Li et al, ; Chen et al, ]. Eps8 is phosphorylated not only by EGFR but also by fibroblast growth factor receptor (FGFR), platelet‐derived growth factor receptor [Fazioli et al, ], and v‐Src [Maa et al, ].…”

“…Overexpression of Eps8 increased serum‐induced ERK activation [Maa et al, ] and Eps8 knockdown decreased ERK activation, and downregulated downstream targets of ERK, such as c‐Myc and cyclin D1 in MDA‐MB‐231 breast cancer cells [Chen et al, ]. Eps8 interacts with FAK at focal adhesions in skin squamous cell carcinoma cells [Schoenherr et al, ] and enhances expression and phosphorylation of FAK, leading to increased proliferation and migration of colon cancer cells [Maa et al, ].…”

LncRNA DSCAM‐AS1 acts as a sponge of miR‐137 to enhance Tamoxifen resistance in breast cancer

“…Accumulated studies have identified the EPS8 as a target gene in the modulation process in cancerous cells. A latest research has proved the effect of overexpression of EPS8 on cell reproduction, and metastasis in human breast cancers via regulation of ERK signaling, MMP9, p53, and EMT‐like transition (Chen et al, ). Mitra et al (Mitra, Lee, Cantrell, & Van den berg, ) found that c‐Jun N‐terminal kinase 2 (JNK2) enhances cell migration via EPS8.…”

A hypoxic signature marks tumors formed by disseminated tumor cells in the BALB-neuT mammary cancer model

“…Besides a hypoxic profile, DTC tumors also have marked expression of cancer relevant genes (Table 3) such as the metastasis-promoting tetraspanin 8 ( TSPAN8 ) [43], proliferation and migration promoting epidermal growth factor substrate 8 ( EPS8 ) [44, 45]. These results suggest that the DTC tumor phenotype could endow them with enhanced aggressiveness; indeed, it would be interesting to examine whether this phenotype might constitute a prerequisite for metastasis formation in this mouse model.…”