WNT Signaling in Neuroblastoma

Abstract

The term WNT (wingless-type MMTV integration site family) signaling comprises a complex molecular pathway consisting of ligands, receptors, coreceptors, signal transducers and transcriptional modulators with crucial functions during embryonic development, including all aspects of proliferation, morphogenesis and differentiation. Its involvement in cancer biology is well documented. Even though WNT signaling has been divided into mainly three distinct branches in the past, increasing evidence shows that some molecular hubs can act in various branches by exchanging interaction partners. Here we discuss developmental and clinical aspects of WNT signaling in neuroblastoma (NB), an embryonic tumor with an extremely broad clinical spectrum, ranging from spontaneous differentiation to fatal outcome. We discuss implications of WNT molecules in NB onset, progression, and relapse due to chemoresistance. In the light of the still too high number of NB deaths, new pathways must be considered.

Keywords: cancer; development; embryonic; neural crest; sympathetic.

Figure 1

Transverse section of a chick day-2 embryo showing migration of neural crest cells (arrows) from the neural tube (Nt). Ao: Aorta; N: Notochord: So: Somites.

Figure 2

WNT pathway molecules and their involvement in chemoresistance in NB. For detailed, information please see text.

Figure 3

Synthesis of β-catenin involvement in NB as provided by several authors. Blue: [68]; purple: [66]; yellow: [17,18,91,92]; brown: [93]; green: [88]; orange: [70]; red: [67]. For detailed information please see text.