Alternative TrkAIII splicing: A potential regulated tumor-promoting switch and therapeutic target in neuroblastoma

Antonella Tacconelli, Antonietta R. Farina, Lucia Cappabianca, Alberto Gulino, Andrew R. Mackay

Research output: Contribution to journalArticle

Abstract

An association between elevated tyrosine kinase receptor (Trk)-A expression and better prognosis; the absence of mutation-activated TrkA oncogenes; the induction of apoptosis, growth arrest, morphological differentiation and inhibition of xenograft growth; and angiogenesis by TrkA gene transduction, provide the basis for the current concept of an exclusively tumor-suppressor role for TrkA in the aggressive pediatric tumor, neuroblastoma. This concept, however, has recently been challenged by the discovery of a novel hypoxia-regulated alternative TrkAIII splice variant, initial data for which suggest predominant expression in advanced-stage neuroblastoma. TrkAIII exhibits neuroblastoma xenograft tumor-promoting activity associated with the induction of a more angiogenic and stress-resistant neuroblastoma phenotype and antagonises nerve growth factor/TrkAI antioncogenic signaling. In this short review, the authors integrate this novel information into a modified concept that places alternative TrkA splicing as a potential pivotal regulator of neuroblastoma behavior and identifies the TrkAIII alternative splice variant as a potential biomarker of patient prognosis and novel therapeutic target.

Original languageEnglish
Pages (from-to)689-698
Number of pages10
JournalFuture Oncology
Volume1
Issue number5
DOIs
Publication statusPublished - Oct 2005

Keywords

  • alternative splicing
  • angiogenesis
  • hypoxia
  • immunoglobulinlike domain
  • neuroblastoma
  • novel therapeutic target
  • PI3k/Akt/NF?B
  • Ras/MAPK
  • survival
  • tumor progression
  • Tyrosine kinase receptor AIII

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Alternative TrkAIII splicing: A potential regulated tumor-promoting switch and therapeutic target in neuroblastoma'. Together they form a unique fingerprint.

  • Cite this