Kidins220/ARMS: A Novel Regulator of Cell Differentiation in Neuroblastoma
Kidins220/ARMS is a recently characterized protein which has been shown to be a substrate for phosphorylation by TrkA and TrkB receptors. After phosphorylation, Kidins220/ARMS acts as a scaffold for the MAPK signaling cascade.
Neuroblastoma is a PNS tumor that is derived from the neuroblasts of neural crest origin. The expression of TrkA and TrkB is strongly correlated to the aggressiveness of the tumor and is used as a prognostic factor. Because Kidins220/ARMS can affect the signaling of neurotrophic receptors, we hypothesize that Kidins220/ARMS could be used to affect the proliferation or survival of neuroblastoma.
Our early results show that neuroblastoma cell lines and primary tumors express Kidins220/ARMS. The knockdown of Kidins220/ARMS changes the morphology of the SH-SY5Y cells, which correlates with loss of doublecortin expression, a marker of immature neurons. Reintroducing Kidins220/ARMS into the cells causes doublecortin to be expressed again. Because Kidins220/ARMS is important in the differentiation of the SH-SY5Y cell line, we are investigating further the signaling pathways that modulate these changes and determining if this signaling system can be targeted in the clinical setting.