Hyaluronan-mediated motility receptor

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Hyaluronan-mediated motility receptor (RHAMM)
Identifiers
Symbols HMMR ; CD168; IHABP; RHAMM
External IDs OMIM600936 MGI104667 HomoloGene8271 GeneCards: HMMR Gene
RNA expression pattern
PBB GE HMMR 209709 s at tn.png
PBB GE HMMR 207165 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3161 15366
Ensembl ENSG00000072571 ENSMUSG00000020330
UniProt O75330 Q00547
RefSeq (mRNA) NM_001142556 NM_013552
RefSeq (protein) NP_001136028 NP_038580
Location (UCSC) Chr 5:
162.89 – 162.92 Mb
Chr 11:
40.7 – 40.73 Mb
PubMed search [1] [2]

Hyaluronan-mediated motility receptor (RHAMM), also known as HMMR and IHABP is a protein which in humans is encoded by the HMMR gene.[1] RHAMM recently has been designated CD168 (cluster of differentiation 168).

Function[edit]

RHAMM was originally discovered as a soluble protein that altered migratory cell behavior and bound to hyaluronan,[2] RHAMM is less well studied than the main hyaluronan (HA) receptor, CD44. In contrast to CD44 and other cell-surface receptors which contain the classical membrane spanning domain and signal sequence for secretion from the endoplasmic reticulum / Golgi complex, RHAMM does not contain a membrane spanning domain nor does the mRNA transcript contain a signal sequence. RHAMM normally is localized inside the cell and is only release by certain, poorly defined stimuli. The transport of RHAMM to the extracellular space still is unclear but may involve transport channels or proteins, flippase activity, or exocytosis.[3]

Intracellularly, RHAMM associates with microtubules and, working with BRCA1 and BARD1, plays a role in the regulation of mitosis.[4][5][6] Extracellularly, RHAMM associates with CD44, and upon binding to HA, activates intracellular signaling pathways.[7] Variants of RHAMM caused by alternative splicing have been observed, but not thoroughly studied.

Clinical significance[edit]

Preliminary reports have suggested that alternatively spliced forms of RHAMM may be upregulated in some tumor types, promoting tumor progression.[8]

Furthermore, the receptor for hyaluronan mediated motility has been reported to mediate migration, transformation, and metastatic spread of murine fibroblasts.[1]

While RHAMM has been less studied than CD44 in the process of cancer metastasis, the research that has been produced shows that it is likely just as important in this process and probably plays a larger role in cell motility than CD44. Increased RHAMM expression is correlated with metastases in colorectal cancer, among others.[9] Mechanistically, RHAMM has been shown to promote cell motility through a number of different pathways. As with CD44, RHAMM can promote focal adhesion turnover by controlling focal adhesion kinase (FAK) phosphorylation and cooperating with the α4β1 and α5β1 integrins.[10] RHAMM also activates a number of downstream kinases including Erk 1/2 through the Map Kinase (MAPK) pathway, pp60 (c-src), and the downstream targets of Rho Kinase (ROK).[11] Finally, once a metastatic lesion has been established, RHAMM can cooperate with CD44 to promote angiogenesis by promoting migration of neighboring endothelial cells towards the tumor.[12]

References[edit]

  1. ^ a b "Entrez Gene: HMMR hyaluronan-mediated motility receptor (RHAMM)". 
  2. ^ Turley EA (October 1982). "Purification of a hyaluronate-binding protein fraction that modifies cell social behavior". Biochem. Biophys. Res. Commun. 108 (3): 1016–24. doi:10.1016/0006-291X(82)92101-5. PMID 6185115. 
  3. ^ Maxwell CA, McCarthy J, Turley E (April 2008). "Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?". J. Cell. Sci. 121 (Pt 7): 925–32. doi:10.1242/jcs.022038. PMID 18354082. 
  4. ^ Maxwell CA, Keats JJ, Crainie M, Sun X, Yen T, Shibuya E, Hendzel M, Chan G, Pilarski LM (June 2003). "RHAMM Is a Centrosomal Protein That Interacts with Dynein and Maintains Spindle Pole Stability". Mol. Biol. Cell 14 (6): 2262–76. doi:10.1091/mbc.E02-07-0377. PMC 194876. PMID 12808028. 
  5. ^ Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, Walter JC, Livingston DM. (2006). "The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly". Cell 127 (3): 539–52. doi:10.1016/j.cell.2006.08.053. PMID 17081976. 
  6. ^ Pujana MA, Han JD, Starita LM, Stevens KN, Tewari M, Ahn JS, Rennert G, Moreno V, Kirchhoff T, Gold B, Assmann V, Elshamy WM, Rual JF, Levine D, Rozek LS, Gelman RS, Gunsalus KC, Greenberg RA, Sobhian B, Bertin N, Venkatesan K, Ayivi-Guedehoussou N, Solé X, Hernández P, Lázaro C, Nathanson KL, Weber BL, Cusick ME, Hill DE, Offit K, Livingston DM, Gruber SB, Parvin JD, Vidal M. (2007). "Network modeling links breast cancer susceptibility and centrosome dysfunction". Nat Genet 39 (11): 1338–49. doi:10.1038/ng.2007.2. PMID 17922014. 
  7. ^ Turley EA, Austen L, Vandeligt K, Clary C (March 1991). "Hyaluronan and a cell-associated hyaluronan binding protein regulate the locomotion of ras-transformed cells". J. Cell Biol. 112 (5): 1041–7. doi:10.1083/jcb.112.5.1041. PMC 2288867. PMID 1705559. 
  8. ^ Crainie M, Belch AR, Mant MJ, Pilarski LM (March 1999). "Overexpression of the receptor for hyaluronan-mediated motility (RHAMM) characterizes the malignant clone in multiple myeloma: identification of three distinct RHAMM variants". Blood 93 (5): 1684–96. PMID 10029598. 
  9. ^ Li H, Guo L, Li J, Liu N, Liu J (October 2000). "Alternative splicing of RHAMM gene in chinese gastric cancers and its in vitro regulation". Zhonghua Yi Xue Yi Chuan Xue Za Zhi (in Chinese) 17 (5): 343–7. PMID 11024216. 
  10. ^ Hall CL, Wang C, Lange LA, Turley EA (July 1994). "Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity". J. Cell Biol. 126 (2): 575–88. doi:10.1083/jcb.126.2.575. PMC 2200030. PMID 7518470. 
  11. ^ Hamilton SR, Fard SF, Paiwand FF, Tolg C, Veiseh M, Wang C, McCarthy JB, Bissell MJ, Koropatnick J, Turley EA (June 2007). "THE HYALURONAN RECEPTORS CD44 AND RHAMM (CD168) FORM COMPLEXES WITH ERK1,2, WHICH SUSTAIN HIGH BASAL MOTILITY IN BREAST CANCER CELLS". J. Biol. Chem. 282 (22): 16667–80. doi:10.1074/jbc.M702078200. PMC 2949353. PMID 17392272. 
  12. ^ Savani RC, Cao G, Pooler PM, Zaman A, Zhou Z, DeLisser HM (September 2001). "Differential involvement of the hyaluronan (HA) receptors CD44 and receptor for HA-mediated motility in endothelial cell function and angiogenesis". J. Biol. Chem. 276 (39): 36770–8. doi:10.1074/jbc.M102273200. PMID 11448954. 

Further reading[edit]

  • Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
  • Hall CL, Yang B, Yang X et al. (1995). "Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation". Cell 82 (1): 19–26. doi:10.1016/0092-8674(95)90048-9. PMID 7541721. 
  • Pilarski LM, Miszta H, Turley EA (1993). "Regulated expression of a receptor for hyaluronan-mediated motility on human thymocytes and T cells". J. Immunol. 150 (10): 4292–302. PMID 7683315. 
  • Spicer AP, Roller ML, Camper SA et al. (1996). "The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11". Genomics 30 (1): 115–7. doi:10.1006/geno.1995.0022. PMID 8595891. 
  • Wang C, Entwistle J, Hou G et al. (1996). "The characterization of a human RHAMM cDNA: conservation of the hyaluronan-binding domains". Gene 174 (2): 299–306. doi:10.1016/0378-1119(96)00080-7. PMID 8890751. 
  • Assmann V, Marshall JF, Fieber C et al. (1999). "The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells". J. Cell. Sci. 111 (12): 1685–94. PMID 9601098. 
  • Pilarski LM, Pruski E, Wizniak J et al. (1999). "Potential role for hyaluronan and the hyaluronan receptor RHAMM in mobilization and trafficking of hematopoietic progenitor cells". Blood 93 (9): 2918–27. PMID 10216086. 
  • Assmann V, Jenkinson D, Marshall JF, Hart IR (2000). "The intracellular hyaluronan receptor RHAMM/IHABP interacts with microtubules and actin filaments". J. Cell. Sci. 112 (22): 3943–54. PMID 10547355. 
  • Lokeshwar VB, Selzer MG (2000). "Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells". J. Biol. Chem. 275 (36): 27641–9. doi:10.1074/jbc.M003084200. PMID 10882722. 
  • Lynn BD, Li X, Cattini PA, Nagy JI (2001). "Sequence, protein expression and extracellular-regulated kinase association of the hyaladherin RHAMM (receptor for hyaluronan mediated motility) in PC12 cells". Neurosci. Lett. 306 (1–2): 49–52. doi:10.1016/S0304-3940(01)01870-5. PMID 11403955. 
  • Lynn BD, Turley EA, Nagy JI (2001). "Subcellular distribution, calmodulin interaction, and mitochondrial association of the hyaluronan-binding protein RHAMM in rat brain". J. Neurosci. Res. 65 (1): 6–16. doi:10.1002/jnr.1122. PMID 11433424. 
  • Savani RC, Cao G, Pooler PM et al. (2001). "Differential involvement of the hyaluronan (HA) receptors CD44 and receptor for HA-mediated motility in endothelial cell function and angiogenesis". J. Biol. Chem. 276 (39): 36770–8. doi:10.1074/jbc.M102273200. PMID 11448954. 
  • Akiyama Y, Jung S, Salhia B et al. (2002). "Hyaluronate receptors mediating glioma cell migration and proliferation". J. Neurooncol. 53 (2): 115–27. doi:10.1023/A:1012297132047. PMID 11716065. 
  • Greiner J, Ringhoffer M, Taniguchi M et al. (2002). "Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia". Exp. Hematol. 30 (9): 1029–35. doi:10.1016/S0301-472X(02)00874-3. PMID 12225794. 
  • Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Rein DT, Roehrig K, Schöndorf T et al. (2003). "Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis". J. Cancer Res. Clin. Oncol. 129 (3): 161–4. doi:10.1007/s00432-003-0415-0. PMID 12712331. 
  • Maxwell CA, Keats JJ, Crainie M et al. (2004). "RHAMM Is a Centrosomal Protein That Interacts with Dynein and Maintains Spindle Pole Stability". Mol. Biol. Cell 14 (6): 2262–76. doi:10.1091/mbc.E02-07-0377. PMC 194876. PMID 12808028. 
  • Aziz KA (2004). "CD44 mediates polymorphonuclear leukocyte motility on hyaluronan". Saudi medical journal 24 (8): 827–31. PMID 12939665. 
  • Maxwell CA, Keats JJ, Belch AR et al. (2005). "Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity". Cancer Res. 65 (3): 850–60. PMID 15705883. 
  • Yamasaki C, Tashiro S, Nishito Y et al. (2005). "Dynamic cytoplasmic anchoring of the transcription factor Bach1 by intracellular hyaluronic acid binding protein IHABP". J. Biochem. 137 (3): 287–96. doi:10.1093/jb/mvi031. PMID 15809329. 
  • Pujana MA, Han JD, Starita LM et al. (2007). "Network modeling links breast cancer susceptibility and centrosome dysfunction". Nat. Genet. 39 (11): 1338–49. doi:10.1038/ng.2007.2. PMID 17922014. 
  • Kalmyrzaev B, Pharoah PD, Easton DF et al. (2008). "Hyaluronan-mediated motility receptor gene single nucleotide polymorphisms and risk of breast cancer". Cancer Epidemiol Biomarkers Prev. 17 (12): 3618–20. doi:10.1158/1055-9965.EPI-08-0216. PMID 19064580. 

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