ROR1

Last updated

ROR1
Identifiers
Aliases ROR1 , NTRKR1, dJ537F10.1, receptor tyrosine kinase-like orphan receptor 1, receptor tyrosine kinase like orphan receptor 1
External IDs OMIM: 602336; MGI: 1347520; HomoloGene: 3675; GeneCards: ROR1; OMA:ROR1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001083592
NM_005012

NM_013845
NM_001312690

RefSeq (protein)

NP_001077061
NP_005003

NP_001299619
NP_038873

Location (UCSC) Chr 1: 63.77 – 64.18 Mb Chr 4: 99.95 – 100.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6] [7] ROR1 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family.

Contents

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. [5] ROR1 is currently under investigation for its role in the metastasis of cancer cells. [8]

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. [9]

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. [10]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185483 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000035305 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: receptor tyrosine kinase-like orphan receptor 1".
  6. Masiakowski P, Carroll RD (Dec 1992). "A novel family of cell surface receptors with tyrosine kinase-like domain". The Journal of Biological Chemistry. 267 (36): 26181–90. doi: 10.1016/S0021-9258(18)35733-8 . PMID   1334494.
  7. Reddy UR, Phatak S, Pleasure D (Oct 1996). "Human neural tissues express a truncated Ror1 receptor tyrosine kinase, lacking both extracellular and transmembrane domains". Oncogene. 13 (7): 1555–9. PMID   8875995.
  8. Cui B, Zhang S, Chen L, Yu J, Widhopf GF, Fecteau JF, Rassenti LZ, Kipps TJ (June 2013). "Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis". Cancer Research. 73 (12): 3649–60. doi:10.1158/0008-5472.CAN-12-3832. PMC   3832210 . PMID   23771907.
  9. 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 (Dec 2014). "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. Bibcode:2014PNAS..11117266Z. doi: 10.1073/pnas.1419599111 . PMC   4260559 . PMID   25411317.
  10. Wang M, et al. (2022). "Zilovertamab vedotin targeting of ROR1 as therapy for lymphoid cancers" (PDF). NEJM Evidence. 1 (1): EVIDoa2100001. doi:10.1056/EVIDoa2100001. PMID   38319241. S2CID   245430438.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.