WNT signaling, the development of the sympathoadrenal-paraganglionic system and neuroblastoma

Cell Mol Life Sci. 2018 Mar;75(6):1057-1070. doi: 10.1007/s00018-017-2685-8. Epub 2017 Oct 22.


Neuroblastoma (NB) is a tumor of the sympathoadrenal system arising in children under 15 years of age. In Germany, NB accounts for 7% of childhood cancer cases, but 11% of cancer deaths. It originates from highly migratory progenitor cells that leave the dorsal neural tube and contribute neurons and glial cells to sympathetic ganglia, and chromaffin and supportive cells to the adrenal medulla and paraganglia. Clinically, histologically and molecularly, NBs present as extremely heterogeneous, ranging from very good to very poor prognosis. The etiology of NB still remains unclear and needs to be elucidated, however, aberrant auto- and paracrine embryonic cell communications seem to be likely candidates to initiate or facilitate the emergence, progression and regression of NB. The wingless-type MMTV integration site (WNT) family of proteins represents an evolutionary highly conserved signaling system that orchestrates embryogenesis. At least 19 ligands in the human, numerous receptors and co-receptors are known, which control not only proliferation, but also cell polarity, migration and differentiation. Here we seek to interconnect aspects of WNT signaling with sympathoadrenal and paraganglionic development to define new WNT signaling cues in the etiology and progression of NB.

Keywords: Neural crest; Neuroblastoma; Paraganglion; Sympathoadrenal system.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adrenal Gland Diseases / genetics*
  • Adrenal Gland Diseases / metabolism
  • Adrenal Gland Diseases / mortality
  • Adrenal Gland Diseases / pathology
  • Adrenal Glands / growth & development
  • Adrenal Glands / metabolism
  • Adrenal Glands / pathology
  • Child
  • Child, Preschool
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Crest / growth & development
  • Neural Crest / metabolism
  • Neural Crest / pathology
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Paraganglioma / genetics*
  • Paraganglioma / metabolism
  • Paraganglioma / mortality
  • Paraganglioma / pathology
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Survival Analysis
  • Sympathetic Nervous System / growth & development
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / pathology
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics*


  • Nerve Tissue Proteins
  • Wnt Proteins