Outline
- Abstract
- Introduction
- Ror1/2 Functions Within Development
- Ror1 in Cancer
- Prospective
- Notes
- References
- Copyright Information
- About This Article
رئوس مطالب
- چکیده
- کلیدواژه ها
- مقدمه
- عملکرد ROR1 / 2 در توسعه
- ROR1 در سرطان
- ROR1 در بدخیمی های سخت
- ROR1 هدف ایمن درمانی
- چشم انداز
Abstract
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR family consisting of ROR1 and ROR2. RORs contain two distinct extracellular cysteine-rich domains and one transmembrane domain. Within the intracellular portion, ROR1 possesses a tyrosine kinase domain, two serine/threonine-rich domains and a proline-rich domain. RORs have been studied in the context of embryonic patterning and neurogenesis through a variety of homologs. These physiologic functions are dichotomous based on the requirement of the kinase domain. A growing literature has established ROR1 as a marker for cancer, such as in CLL and other blood malignancies. In addition, ROR1 is critically involved in progression of a number of blood and solid malignancies. ROR1 has been shown to inhibit apoptosis, potentiate EGFR signaling, and induce epithelial-mesenchymal transition (EMT). Importantly, ROR1 is only detectable in embryonic tissue and generally absent in adult tissue, making the protein an ideal drug target for cancer therapy.
Keywords: cancer - embryogenesis - immunotherapy - ROR1Prospective
ROR1 is expressed in a number of malignancies with low levels of expression in normal adult tissue. Much like the physiological functions of ROR1, ROR1 in cancer can have kinase activity-dependent or -independent function, which could be a result of tissue specific expression of co-receptor or effector proteins. The induction of apoptosis with ROR1 knockdown, EGFR signaling potentiation and ROR1-mediated upregulation of EMT genes support the notion that ROR1 plays an important role in cancer progression rather than just a bystander. Further research is required to elucidate the tumor-specific mechanisms of ROR1 overexpression and the contribution of ROR1 to initiation and progression of cancer. Furthermore, as an oncofetal protein with absence of expression in most adult tissue, ROR1 represents an ideal druggable target for cancer therapy.