Huntress ror17/20/2023 ![]() ![]() In contrast, other Wnt ligands such as Wnt5a/b and Wnt16 bind to the ROR family proteins and activate β-catenin-independent Wnt/planar cell polarity and Wnt/Ca 2+ pathways, involving activation of small GTPases Rho/Rac signaling proteins and the protein kinase C (PKC)/calcineurin signaling cascade, respectively. This activated signaling cascade stabilizes β-catenin to facilitate transcription of pro-survival genes, including Myc, Survivin, and MMP ( 9– 11). Several Wnt ligands, including Wnt1, Wnt3a, and Wnt8, can bind to the Frizzled family of receptors to trigger the β-catenin-dependent Wnt signaling pathway. ![]() The Wnt family of proteins transduce signals through the canonical β-catenin-dependent and non-canonical β-catenin-independent pathways ( 7, 8). Now it is known that ROR family members are receptors for Wnt family signaling molecules Wnt5a/b and Wnt16, with Wnt5a as the primary ligand ( 3– 6). The ROR subfamily members were designated as “orphan” receptors because their ligands have not been identified for many years. ROR1 and ROR2 are evolutionarily conserved among animals including protostomes, cnidarians, and all vertebrates, suggesting a critical physiological function of ROR family members in development. The receptor tyrosine kinase-like orphan receptor (ROR) subfamily contains two members, namely, ROR1 and ROR2 that were initially identified in a human neuroblastoma cell line in 1992 ( 2). To date, the RTKs superfamily has 58 members that fall into 20 subfamilies. Receptor tyrosine kinases (RTKs) are key regulators of normal cellular processes, and they are also involved in the development and progression of many types of cancer ( 1). In this review, we analyzed the structural and functional features of ROR1 and discussed therapeutic strategies targeting this kinase. The function of ROR1 as a tyrosine kinase remains poorly understood, although accumulating evidence have demonstrated its intrinsic tyrosine kinase activity. However, small molecule inhibitors targeting ROR1 are underappreciated because of the initial characterization of ROR1 as a peusdokinase. Antibody-based immunotherapies targeting ROR1 have been developed and evaluated in preclinical and clinical studies with promising outcomes. Studies have demonstrated that it plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway. Receptor tyrosine kinase ROR1 plays an essential role in embryogenesis and is overexpressed in many types of malignant tumors. 3Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.2Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.Fischer Translational Medical Research Laboratory, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China Yuming Zhao 1†, Dengyang Zhang 1†, Yao Guo 1†, Bo Lu 2, Zhizhuang Joe Zhao 3*, Xiaojun Xu 2* and Yun Chen 1* ![]()
0 Comments
Leave a Reply. |