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.
Highlights
The term WNT 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
It acts by regulating the degradation rates of the transmembrane receptors VANGL1/2, which interact with CLSR2, the human homologue of Drosophila Fmi (Flamingo), to orientate epithelial as well as mesenchymal cells during the development and regeneration by cell-cell interactions according to a WNT gradient [15]
NB is widely accepted as an embryonic developmental malignancy derived from progenitor cells originating from the sympathetic neural crest
Summary
The name WNT is an acronym combining the Int gene (see list of abbreviations at the end of the text) found in mice and the wingless gene from drosophila [1,2]. The receptors LGR4/5/6 and their ligands, the R-spondins, further enhance TCF/LEF-mediated WNT/β-catenin signaling [3,8,9] This pathway is regarded to promote proliferation of cells by activation (or acceleration) of the cell cycle. The PCP pathway is activated by the receptor tyrosine kinases ROR1, ROR2 and RYK, which may act alone, or as co-receptors in conjunction with FZDs (reviewed by [10]). It acts by regulating the degradation rates of the transmembrane receptors VANGL1/2, which interact with CLSR2, the human homologue of Drosophila Fmi (Flamingo), to orientate epithelial as well as mesenchymal cells during the development and regeneration by cell-cell interactions according to a WNT gradient [15].
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