NF-κB acts as a multifunctional modulator in bone invasion by oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral cavity and the head and neck region. Gingival squamous cell carcinomas (SCCs) frequently invade the maxilla or the mandibular bone and are associated with poor prognosis. Recent findings suggest that osteoclasts, rather than OSCC cells, mediate invasion to the bone. Nuclear factor-κB (NF-κB) is constitutively activated in OSCCs and is involved in promoting the invasive characteristics of OSCC. NF-κB activation is also important for receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. NF-κB inhibitors suppress proliferation and stimulate apoptosis of OSCC cells in vitro and in vivo, as well as inhibit matrix metalloproteinase (MMP) production in OSCC. Furthermore, NF-κB inhibitors have been shown to suppress osteoclastogenesis by reducing RANKL expression in animal models. Thus, inhibition of NF-κB activity may constitute a promising therapeutic approach to treat bone-invasive OSCC. In this review, we discuss recent findings, which suggest that bone invasion in OSCC is mediated via NF-κB signaling and may be successfully prevented by NF-κB inhibition.