Receptor tyrosine kinase-like orphan receptor 1 (ROR1) (ROR1)

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type I transmembrane receptor protein approximately 105 kDa in size that plays critical roles in both embryonic development and cancer biology[1][3]. The protein contains extracellular immunoglobulin-like, frizzled, and Kringle domains, along with intracellular tyrosine kinase, serine/threonine-rich, and proline-rich domains[1][3]. While structurally classified as a receptor tyrosine kinase, ROR1 exhibits very low or negligible kinase activity in vitro and functions primarily through non-canonical Wnt/Wnt5a signaling pathways rather than through intrinsic kinase activity[1][3][4]. ROR1 is normally expressed at high levels during embryonic development but shows minimal expression in most postnatal adult tissues, with the notable exception of adipose tissue, endocrine glands, and the gastrointestinal tract[1]. However, ROR1 expression is markedly upregulated in numerous cancers including chronic lymphocytic leukemia, breast cancer, melanoma, ovarian cancer, and gastrointestinal malignancies, where elevated expression correlates with poor prognosis and aggressive disease characteristics[1][2][3]. ROR1 promotes cancer progression through multiple mechanisms including activation of the Akt/NF-κB pathway, YAP/TAZ-mediated transcription of proliferation genes, c-Src activation, and promotion of epithelial-mesenchymal transition, making it a validated therapeutic target for cancer treatment[1][3]. Current therapeutic strategies targeting ROR1 include monoclonal antibodies, antibody-drug conjugates, CAR-T cell therapies, bispecific T-cell engagers, and small-molecule inhibitors, reflecting its importance as an emerging oncology target[1].

Other names

Inactive tyrosine protein kinase transmembrane receptor ROR1Receptor tyrosine kinase-like orphan receptor 1ROR family member 1Dror (Drosophila homolog)

Activation of non-canonical Wnt/Wnt5a signaling through the frizzled (FZD) domain; Regulation of Akt/NF-κB pathway leading to transcription of proliferation-associated genes (Cyclin D1, c-Myc, VEGF, matrix metalloproteinase-9); Activation of YAP/TAZ pathway promoting tumorigenesis and chemotherapy resistance; Recruitment and activation of c-Src phosphorylation; Interaction with DOCK2 and Rac1/2 activation promoting cell migration; Regulation of epithelial-mesenchymal transition (EMT); Modulation of Wnt signaling through interaction with Kringle domain and other receptors.