Figure 5.

An overview of metastasis mechanism used by primary tumor cells to invade healthy cells in locations other than those of originating tissues. ERRα stimulates metastasis extensively through the NF-κB mediated pro-inflammatory cytokine IL-6 activation mediated transition from epithelial to mesenchymal regime. Two notable studies from 2014 and 2018 shed light on ERRα aggravated EMT, with the former by Huang et al (164) reported treatment of A549 NSCLC cells with ERRα inverse agonist, XCT-790 causing suppressed E-cadherin and zonula occludens-1 (noted epithelial markers) and aggravated fibronectin and vimentin (mesenchymal markers), expression. Zhang et al (165) noticed ERRα aggravated NF-κB expression and translocation which in turn activated the pro-inflammatory cytokine, IL-6 expression. Other studies have reported enhanced IL-6 expression in di (2-ethylhexyl) phthalate (DEHP)-induced NSCLC migration and invasion (166,167). Hence, enhanced ERRα modulates the environment around the tumor by enhanced expression of matrix proteins whereby access of chemotherapeutic drugs to the tumor is prevented, resulting in enhanced tumor growth. ERR, estrogen related receptor; NSCLC, non-small cell lung cancer; EMT, epithelial mesenchymal transition; IL, interleukin.