Estrogen-related receptor alpha triggers the proliferation and migration of human non-small cell lung cancer via interleukin-6

Human non-small cell lung cancer (NSCLC) is one of the leading causes of cancer deaths worldwide. Estrogenic signals have been suggested to be important for the growth and metastasis of NSCLC cells. Our present data showed that estrogen-related receptor alpha (ERR), while not ERR or ERR, was significantly elevated in NSCLC cell lines as compared with that in normal bronchial epithelial cell line BEAS-2B. The expression of ERR in clinical NSCLC tissues was significantly greater than that in their matched normal adjacent tissues. Over expression of ERR can trigger the proliferation, migration, and invasion of NSCLC cells, while si-ERR or ERR inhibitor showed opposite effects. ERR can increase the mRNA and protein expression of IL-6, while not IL-8, IL-10, IL-22, VEGF, TGF-, or TNF-, in NSCLC cells. Silence of IL-6 attenuated ERR induced proliferation and cell invasion. Furthermore, our data revealed the inhibition of NF-B, while not ERK1/2 or PI3K/Akt, abolished ERR induced production of IL-6. This might be due to that overexpression of ERR can increase the expression and nuclear translocation of p65 in NSCLC cells. Collectively, our data showed that activation of NF-B/IL-6 is involved in ERR induced migration and invasion of NSCLC cells. It suggested that ERR might be a potential target for NSCLC treatment.