Neurotrophins are a family of growth factors that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4. Among them, BDNF is the most studied due to its high expression in the brain. Over the past two decades, BDNF and its receptor tropomyosin receptor kinase B (TrkB) have been reported to be upregulated in a wide range of tumors. This activated signal stimulates a series of downstream pathways, including phosphoinositide 3-kinase/protein kinase B, Ras-Raf-mitogen activated protein kinase kinase-extracellular signal-regulated kinases, the phospholipase-C- pathway and the transactivation of epidermal growth factor receptor. Activation of these signaling pathways induces oncogenic effects by increasing cancer cell growth, proliferation, survival, migration and epithelial to mesenchymal transition, and decreasing anoikis, relapse and chemotherapeutic sensitivity. The present review summarizes recent findings to discuss the role of BDNF in tumors, the underlying molecular mechanism, targeting Trk receptors for treatment of cancers and its potential risk.
[1]Florida Hosp, Dept Internal Med, Orlando, FL 32803 USA.
[2]Valencia Coll, Dept Biol, Orlando, FL 32825 USA.
[3]Jilin Univ, Dept Radiat Oncol, Hosp 1, Changchun 130021, Jilin, Peoples R China.
[4]Anhui Med Univ, Dept Resp Med, Affiliated Hosp 1, Hefei 230000, Anhui, Peoples R China.
[5]Jilin Univ, Key Lab Pathobiol, Minist Educ, 126 Xinmin St, Changchun 130021, Jilin, Peoples R China.
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