Dusp6 inhibits epithelial-mesenchymal transition in endometrial adenocarcinoma via ERK signaling pathway
Dusp6 inhibits EMT in EAC via regulating ERK pathway
Background: Endometrial adenocarcinoma (EAC) is one of the most diagnosed gynaecological malignancies among female population of the developed countries. DUSP6 is a negative regulator of ERK which is a molecular switch involved in MAPK signaling during the malignancies. DUSP6 was previously found to inhibit tumorigenesis and EMT-associated properties in several cancers, however its exact role in EAC remains unclear. Methods: The level of DUSP6 in EAC cancerous tissues and the adjacent non-cancerous tissues were examined through western-blot and immunohistochemistry analysis. The cell growth, invasion and migration abilities were measured in Ishikawa 3H12 endometrial cancer cell lines with the overexpressing or knocking down DUSP6. Protein levels of EMT-associated markers E-cadherin, N-cadherin and Vimentin were also determined. The impacts of DUSP6 on ERK signaling was assessed based on the level of ERK and p-ERK in the same cell lines overexpressing or knocking down DUSP6. Results: Down-regulation of DUSP6 was observed in EAC compared with the normal controls. The overexpression of DUSP6 significantly attenuated tumor cell growth, invasion, migration abilities and inhibited EMT-associated markers, which is opposite to the results of knock down of DUSP6. The overexpression of DUSP6 also down-regulated p-ERK and the knock down of DUSP6 inversely up-regulated p-ERK. Conclusions: The knockdown of DUSP6 promoted cell growth, invasion and migration abilities in Ishikawa 3H12 cells as well as enhancing EMT-associated properties, which was contrary to the results of overexpressing DUSP6. This suppressive role of DUSP6 during the EMT process in EAC is implemented by inhibiting ERK signaling pathway.