The receptor tyrosine kinase orphan receptor 1 (ROR1) serves as a receptor for WNT5A and related Wnt proteins, which are crucial during embryonic development. They regulate processes such as cell migration, cell polarity, neural patterning, and organogenesis. ROR1 mediates these functions by transducing signals from the Wnt secreted glycoproteins to the intracellular Wnt/PCP and Wnt/Ca++ pathways.
In adult human cells, especially in cancer cells, research has shown that the WNT5A/ROR1 axis can activate a variety of signaling pathways in addition to the aforementioned ones. These include the PI3K/AKT, MAPK, NF-κB, STAT3, and Hippo pathways. Furthermore, ROR1 is often aberrantly expressed in cancer and has been linked to tumor progression and poor patient survival outcomes. Its role in promoting cell proliferation, survival, invasion, epithelial-to-mesenchymal transition (EMT), and metastasis is significant.
As a result, ROR1 has emerged as a potential therapeutic target, and numerous tools aimed at targeting ROR1 are currently under evaluation in clinical trials for cancer patients.