Consideration of EphA2 in relation to epithelial-mesenchymal transition in uterine endometrial cancer.

Abstract

To the editor: For decades, the mechanisms of cancer cell metastasis have been critical subject in the field of cancer research. Among them, the epithelial-mesenchymal transition (Emt) and mesenchymal-epithelial transition (MET) have been, currently, acknowledged as a crucial process by which carcinoma cells are acquired metastatic phenotype such as invasion of vessels and distant colonization, as well as a physiologic process during embryonic development. In the volume 25 January, a research article regarding the correlation between the overexpression of epidermal growth factor receptor (EGFR) and EMT makers in endometrial cancer gave us the result that mesenchymal markers (N-cadherin and vimentin) was overexpressed in advanced stage and high grade tissue specimens of patients and also the upregulation of mesenchymal markers was observed in KLE cells and Ishikawa cells transfected with EGFR [1]. EphA2, a member of the biggest subfamily of RTKs, could be recognized as a molecular target based on the growing evidence that high levels of it promote various aspects of malignant phenotype, including proliferation, invasion, angiogenesis and survival of cancer cells. My previous research showed that high EphA2 expression and high angiogenesis makers were significantly associated with shorter disease-specific survival in tissue specimens of patients with endometrial cancer, and also the therapy using EphA2 agonist monoclonal antibody led to tumor inhibition over controls in murine orthotopic xenograft model made by Hec1A and Ishikawa cells [2]. Interestingly, several research papers regarding the correlation between EphA2 and EMT were currently published. Huang et al. [3] reported that EphA2 promotes EMT in gastric cancer cells and demonstrated that the promoting effect of EphA2 on EMT was made through the Wnt/β-catenin pathway based on the experiments employing the inhibitor and activator of that pathway. Additionally, Giannoni et al. [4] reported that mesenchymal-amoeboid transition, a second type of motility shifting process in cancer cells induced by endothelial progenitor cells, was mediated through the bidirectional ephrinA1/EphA2 signaling. Thereby, EphA2 could be also considered as a regulator in relation to epithelialmesenchymal transition in endometrial cancer.