ROR1 explained

Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is an enzyme that in humans is encoded by the ROR1 gene.^{[1] [2] [3]} ROR1 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family.

Function

The protein encoded by this gene is a receptor tyrosine kinase that modulates neurite growth in the central nervous system. It is a type I membrane protein and belongs to the ROR subfamily of cell surface receptors.^[1] ROR1 is currently under investigation for its role in the metastasis of cancer cells.^[4]

ROR1 has recently been shown to be expressed on ovarian cancer stem cell, on which it seems to play a functional role in promoting migration/invasion or spheroid formation in vitro and tumor engraftment in immune-deficient mice. Treatment with a humanized mAb specific for ROR1 (UC-961) could inhibit the capacity of ovarian cancer cells to migrate, form spheroids, or engraft immune-deficient mice. Moreover, such treatment inhibited the growth of tumor xenografts, which in turn had a reduced capacity to engraft immune-deficient mice and were relatively depleted of cells with features of CSC, suggesting that treatment with UC-961 could impair CSC renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which may be targeted for anti-CSC therapy.^[5]

Zilovertamab vedotin (ZV), an antibody–drug conjugate comprising a monoclonal antibody recognizing extracellular ROR1, a cleavable linker and monomethyl auristatin E has entered clinical trials for the treatment of lymphoid malignancies.^[6]

Further reading

• Reddy UR, Phatak S, Allen C, Nycum LM, Sulman EP, White PS, Biegel JA . Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis . Genomics . 41 . 2 . 283–5 . Apr 1997 . 9143508 . 10.1006/geno.1997.4653 . free .
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR . Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score . Molecular Medicine . 2010 . 16 . 7–8 . 247–53 . 20379614 . 2896464 . 10.2119/molmed.2009.00159 .
• Nomi M, Oishi I, Kani S, Suzuki H, Matsuda T, Yoda A, Kitamura M, Itoh K, Takeuchi S, Takeda K, Akira S, Ikeya M, Takada S, Minami Y . Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2-deficient mice: redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases . Molecular and Cellular Biology . 21 . 24 . 8329–35 . Dec 2001 . 11713269 . 99997 . 10.1128/MCB.21.24.8329-8335.2001 .
• Baskar S, Kwong KY, Hofer T, Levy JM, Kennedy MG, Lee E, Staudt LM, Wilson WH, Wiestner A, Rader C . Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia . Clinical Cancer Research . 14 . 2 . 396–404 . Jan 2008 . 18223214 . 10.1158/1078-0432.CCR-07-1823 . free .
• Shabani M, Asgarian-Omran H, Omran HA, Jeddi-Tehrani M, Vossough P, Faranoush M, Sharifian RA, Toughe GR, Kordmahin M, Khoshnoodi J, Roohi A, Tavoosi N, Mellstedt H, Rabbani H, Shokri F . Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia . Tumour Biology . 28 . 6 . 318–26 . 2007 . 18354269 . 10.1159/000121405 . 82261 .
• Daneshmanesh AH, Mikaelsson E, Jeddi-Tehrani M, Bayat AA, Ghods R, Ostadkarampour M, Akhondi M, Lagercrantz S, Larsson C, Osterborg A, Shokri F, Mellstedt H, Rabbani H . Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy . International Journal of Cancer . 123 . 5 . 1190–5 . Sep 2008 . 18546292 . 10.1002/ijc.23587 . free .
• Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zöllner S, Schork NJ, Kelsoe JR . Genome-wide association study of bipolar disorder in European American and African American individuals . Molecular Psychiatry . 14 . 8 . 755–63 . Aug 2009 . 19488044 . 3035981 . 10.1038/mp.2009.43 .
• Paganoni S, Ferreira A . Neurite extension in central neurons: a novel role for the receptor tyrosine kinases Ror1 and Ror2 . Journal of Cell Science . 118 . Pt 2 . 433–46 . Jan 2005 . 15654020 . 1351101 . 10.1242/jcs.01622 .
• Shabani M, Asgarian-Omran H, Vossough P, Sharifian RA, Faranoush M, Ghragozlou S, Khoshnoodi J, Roohi A, Jeddi-Tehrani M, Mellstedt H, Rabbani H, Shokri F . Expression profile of orphan receptor tyrosine kinase (ROR1) and Wilms' tumor gene 1 (WT1) in different subsets of B-cell acute lymphoblastic leukemia . Leukemia & Lymphoma . 49 . 7 . 1360–7 . Jul 2008 . 18604725 . 10.1080/10428190802124000 . 22958582 .
• Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ . Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a . Proceedings of the National Academy of Sciences of the United States of America . 105 . 8 . 3047–52 . Feb 2008 . 18287027 . 2268582 . 10.1073/pnas.0712148105 . 2008PNAS..105.3047F . free .

Notes and References

1. Web site: Entrez Gene: receptor tyrosine kinase-like orphan receptor 1.
2. Masiakowski P, Carroll RD . A novel family of cell surface receptors with tyrosine kinase-like domain . The Journal of Biological Chemistry . 267 . 36 . 26181–90 . Dec 1992 . 10.1016/S0021-9258(18)35733-8 . 1334494 . free .
3. Reddy UR, Phatak S, Pleasure D . Human neural tissues express a truncated Ror1 receptor tyrosine kinase, lacking both extracellular and transmembrane domains . Oncogene . 13 . 7 . 1555–9 . Oct 1996 . 8875995 .
4. Cui B, Zhang S, Chen L, Yu J, Widhopf GF, Fecteau JF, Rassenti LZ, Kipps TJ . Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis . Cancer Research . 73 . 12 . 3649–60 . June 2013 . 23771907 . 3832210 . 10.1158/0008-5472.CAN-12-3832 .
5. Zhang S, Cui B, Lai H, Liu G, Ghia EM, Widhopf GF, Zhang Z, Wu CC, Chen L, Wu R, Schwab R, Carson DA, Kipps TJ . Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy . Proceedings of the National Academy of Sciences of the United States of America . 111 . 48 . 17266–71 . Dec 2014 . 25411317 . 10.1073/pnas.1419599111 . 4260559. 2014PNAS..11117266Z . free .
6. Wang M, etal . Zilovertamab vedotin targeting of ROR1 as therapy for lymphoid cancers. NEJM Evidence. 2022 . 1 . 1 . EVIDoa2100001 . 10.1056/EVIDoa2100001 . 38319241 . 245430438 .