Tumor metastasis: induced by the Ro(a)ring of Wnt proteins

Abstract

Abstract Tumor metastases account for approximately 90% of deaths that are caused by cancer. However, their underlying molecular mechanisms are not completely understood and therefore further research on the molecular pathways that are involved in the metastasis of cancer cells is required. Polarized cell migration plays an important role in tumor metastasis, but also in a variety of processes that take place during embryonic development. The non-canonical Wnt signaling pathway is involved in many developmental processes, including epithelial-mesenchymal transition, cell migration and cell polarity. Interestingly, all of these processes are also involved in the development of tumor metastasis and aberrant non-canonical Wnt signaling is frequently observed in metastatic cancer cells. The non-canonical Wnt signaling pathway is activated by the binding of a Wnt ligand called Wnt5a to the receptor tyrosine kinase-like orphan receptor (Ror) at the cell membrane. This leads to the initiation of a signaling cascade that causes multiple downstream effects, including the reorientation of the microtubule-organizing center, the formation of filopodia and lamellipodia, membrane retraction, and the degradation of the extracellular matrix. Ultimately, these downstream effects of the non-canonical Wnt signaling pathway increase polarized cell migration and therefore it is not surprising that disturbed non-canonical Wnt signaling is associated with tumor metastasis. In this thesis, I describe the key players and signaling events of the non-canonical signaling pathway that may contribute to the development of tumor metastasis.