NAG7 promotes human nasopharyngeal carcinoma invasion through inhibition of estrogen receptor alpha and up-regulation of JNK2/AP-1/MMP1 pathways.

The NAG7, an estrogen receptor repressor, is a negative regulator of nasopharyngeal carcinoma cell growth. Here, we report that NAG7 promotes human nasopharyngeal carcinoma invasion, and we identify the mechanisms underlying this function. As a consequence of elevated NAG7 expression, the adhesion, migration, and invasive capabilities of HNE1 cells in vitro and in vivo were enhanced. NAG7 was a significant negative regulator of protein expression of estrogen receptor alpha (ERα), and activated both the JNK2/AP-1/MMP1 and the upstream H-Ras/p-c-Raf pathways. None of these effects induced by NAG7 over-expression could be counteracted by estrogen. These observations indicate that NAG7 plays a potential role in promoting nasopharyngeal carcinoma invasion by regulation of ERα and the H-ras/p-c-Raf and JNK2/AP-1/MMP1 signaling pathways. J. Cell. Physiol. 221: 394–401, 2009. © 2009 Wiley-Liss, Inc.