Ninjurin1 suppresses metastatic property of lung cancer cells through inhibition of interleukin 6 signaling pathway

Abstract

Nerve injury-induced protein 1 (Ninjurinl, Ninjl) is a cell surface molecule that can mediate homophilic adhesion and promote neurite outgrowth from cultured dorsal root ganglion (DRG) neurons. Interestingly, Ninjl overexpressed in human cancer; however, its role in metastasis is not clear. This study showed that inhibition of Ninjl promotes lung cancer metastasis through interleukin 6 (IL-6)/STAT3 signaling. Ninjl levels were relatively low in highly motile lung cancer cells. While inhibition of Ninjl enhanced cell migration in lung cancer cells, overexpression of Ninji significantly suppressed it. We found that inhibition of Ninj1 significantly increased expression and secretion of IL-6 in A549 cells. We also found that inhibition of IL-6 decreased intercellular adhesion molecule 1 (ICAM-1) expression. In addition, inhibition of Ninjl significantly increased cell motility and invasiveness of lung cancer cells. In an in vivo model, we found that Ninjl suppression did not affect tumor growth but induced significant increase in incidence of lung metastasis, and sizes and number of tumor nodules. Taken together, our data clearly demonstrate that Ninjl suppresses migration, invasion and metastasis of lung cancer via inhibition of the IL-6 signaling pathway in vitro and in vivo.