02 BOOK OF ABSTRACTS .indd

TrkAIII: A tumor promoting switch of potential
importance in Neuroblastoma and Glioblastoma
mutliforme
Antonella Tacconelli 1 , Antonietta R. Farina 1 , Lucia Cappabianca 1 ,
Isabella Screpanti 2 , Alberto Gulino 2 and Andrew R. Mackay 1
1
Dept. of Experimental Medicine, University of L’Aquila, L’Aquila, Italy; 2 Dept. of
Experimental Medicine and Pathology, University of Rome “La Sapienza”, Rome, Italy
The discovery of a novel hypoxia-regulated alternative TrkAIII splice variant has
challenged the current concept of an exclusively tumor-suppressor role for TrkA in
the aggressive paediatric tumor, Neuroblastoma (NB). TrkAIII, initial data for which
suggests predominant expression in advanced stage NB, is devoid of exons 6 and 7,
omitting extracellular IgGC1 domain and several N-glycosylation sites of functional
importance. In NB cells TrkAIII exhibits spontaneous activity, signals through
PI3K/Akt/NFκB but not Ras/MAPK, antagonises NGF/TrkAI anti-oncogenic signalling
through Ras/MAPK and promotes NB tumorigenic and metastatic capacity in vivo.
The mechanisms through which TrkAIII exerts its tumor and metastasis promoting
activity will be discussed, as will the extension of our observations to Glioblastoma
multiforme.
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