Role of Tropomyosin-related kinase B receptor and brain-derived neurotrophic factor in cancer

Cytokine. 2020 Dec:136:155270. doi: 10.1016/j.cyto.2020.155270. Epub 2020 Sep 7.

Abstract

The tropomyosin-related kinase B (TrkB) receptor is a member of the neurotrophic tyrosine kinase receptors family and, together with the brain-derived neurotrophic factor (BDNF), plays an important role in the development of breast cancer, lung cancer, neuroblastoma, colorectal cancer, leukemia, cervical cancer, gallbladder cancer, gastric cancer, kidney cancer, Ewing's sarcoma, esophageal cancer, and head and neck cancer. Overexpression of these two factors has been associated with increased processes involved in carcinogenesis, such as invasion, migration, epithelial-mesenchymal transition (EMT), angiogenesis, metastasis, cell proliferation, resistance to apoptosis, resistance to cell death due to loss of adhesion (anoikis), activation of cell proliferation pathways, regulation of tumor suppressor genes, and drug resistance, and is related to advanced clinical stage. Inhibition of the TrkB/BDNF axis using drugs in phase 1 studies, approved drugs, and small interfering RNA (siRNA) are promising strategies for the treatment of various malignant tumors in addition to increasing the sensitivity of cells resistant to chemotherapy, improving the effectiveness of drugs without increasing toxicity. Another factor related to poor cancer prognosis is the presence of cancer stem cells, having effects similar to the high expression of the TrkB/BDNF axis, on cancer. This review aimed to show the role of the TrkB/BDNF axis in several types of cancer, its possible use as a prognostic biomarker, the effects of inhibiting this axis, and its role in the cancer stem cells.

Keywords: Brain-derived neurotrophic factor; Cancer stem cell; Neoplasm; TrkB receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Clinical Trials, Phase I as Topic
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Neoplasm Proteins / metabolism*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Receptor, trkB / metabolism*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human