Neurotrophin signaling in cancer stem cells

Cell Mol Life Sci. 2016 May;73(9):1859-70. doi: 10.1007/s00018-016-2156-7. Epub 2016 Feb 17.

Abstract

Cancer stem cells (CSCs), are thought to be at the origin of tumor development and resistance to therapies. Thus, a better understanding of the molecular mechanisms involved in the control of CSC stemness is essential to the design of more effective therapies for cancer patients. Cancer cell stemness and the subsequent expansion of CSCs are regulated by micro-environmental signals including neurotrophins. Over the years, the roles of neurotrophins in tumor development have been well established and regularly reviewed. Especially, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are reported to stimulate tumor cell proliferation, survival, migration and/or invasion, and favors tumor angiogenesis. More recently, neurotrophins have been reported to regulate CSCs. This review briefly presents neurotrophins and their receptors, summarizes their roles in different cancers, and discusses the emerging evidence of neurotrophins-induced enrichment of CSCs as well as the involved signaling pathways.

Keywords: Epithelial-mesenchymal transition; P75NTR; Signaling pathways; TrkA; TrkB; Tumor initiating cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Epithelial-Mesenchymal Transition
  • Humans
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism*
  • Nerve Growth Factors / metabolism*
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction

Substances

  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Receptors, Nerve Growth Factor