Signaling Transduction Network Mediated by Tumor Suppressor/Susceptibility Genes in NPC

Minghua      Wu; Xiayu      Li; Xiaoling      Li; Guiyuan      Li

Abstract

Nasopharyngeal carcinoma (NPC) is a polygenetic disease. SPLUNC1, UBAP1, BRD7, NAG7, NOR1, NGX6 and LTF genes were found to be tumor suppressor/susceptibility genes in different stages of NPC. SPLUNC1, an early warning molecular diagnosis marker, inhibits the bacteria clone formation, and is an innated immune molecule. SPLUNC1 can negatively regulate the ERK/MAPK signaling transduction pathway to inhibit NPC cell proliferation and induce apoptosis. BRD7, a transcript regulation factor, interacts with BRD2, and promotes apoptosis induced by BRD2. Its promoter is regulated by c-Myc and SP1. BRD7 inhibits NPC cell cycle progression, preventing passage through G0/G1 by suppressing ras/MEK/ERK, Rb/E2F and Wnt signaling pathways. Abnormal activation of BRD7 is crucial to cell cycle turbulence in NPC. NGX6, a metastasis-associated protein, can negative-regulate the EGF/Ras/MAPK signaling transduction pathway, and interacts with ezrin protein to inhibit NPC cell invasion and metastasis. LTF, also a metastasisassociated protein, can negatively regulate MAPK signal transduction pathways, such as JNK2 and ERK, to inhibit NPC cell proliferation and growth. Taken together, it was found that these tumor suppressor/susceptibility genes can regulate key molecules involved in cell signal pathways such as ras/MEK/ERK, Rb/E2F and EGFR ras/MEK/MAPK, and can regulate the expression of some adhesion molecules such as ezrin, nm23 and α-catenin. According to functional genomics and signaling transduction pathways, we have described a signaling cross-talk network between the tumor suppressor/ susceptibility genes involved in NPC. These tumor suppressor/susceptibility genes may be potential treatment targets for NPC in the future.