ABCB5

ATP-binding cassette, sub-family B (MDR/TAP), member 5
Identifiers
Symbols ABCB5; ABCB5alpha; ABCB5beta; EST422562
External IDs OMIM611785 HomoloGene83488 GeneCards: ABCB5 Gene
Orthologs
Species Human Mouse
Entrez 340273 77706
Ensembl ENSG00000004846 ENSMUSG00000072791
UniProt Q2M3G0 n/a
RefSeq (mRNA) NM_001163941.1 NM_029961.2
RefSeq (protein) NP_001157413.1 NP_084237.1
Location (UCSC) Chr 7:
20.65 – 20.82 Mb
Chr 12:
120.11 – 120.2 Mb
PubMed search [1] [2]

ATP-binding cassette sub-family B member 5 also known as P-glycoprotein ABCB5 is a plasma membrane-spanning protein that in humans is encoded by the ABCB5 gene.[1][2] ABCB5 is an ABC transporter and P-glycoprotein family member principally expressed in physiological skin and human malignant melanoma.[3][4]

ABCB5 regulates skin progenitor cell fusion and mediates chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma, and is over-expressed on circulating melanoma tumor cells, suggestive of a metastatic role.[5][6] Furthermore, the ABCB5+ melanoma- initiating cells were demonstrated to express FLT1 (VEGFR1) receptor tyrosine kinase which was functionally required for efficient xenograft tumor formation, as demonstrated by shRNA knockdown experiments.[7]

More recently, the ABCB5 molecule has been shown to be functionally relevant to carcinogenesis, demonstrated in colorectal cancer where it was shown to act as a mediator of 5-FU patient chemoresistance, and had a further direct role in tumorigenesis shown by shRNA-mediated colorectal cancer cell-line ABCB5 knockdowns that impeded tumorigenesis in human-to-mouse xenografts.[8] These data revealed multiple roles for ABCB5 in cancer progression and chemoresistance, making it an attractive target for combined therapy.

References

  1. ^ Allikmets R, Gerrard B, Hutchinson A, Dean M (October 1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum. Mol. Genet. 5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID 8894702. 
  2. ^ Frank NY, Pendse SS, Lapchak PH, Margaryan A, Shlain D, Doeing C, Sayegh MH, Frank MH (November 2003). "Regulation of progenitor cell fusion by ABCB5 P-glycoprotein, a novel human ATP-binding cassette transporter". J. Biol. Chem. 278 (47): 47156–65. doi:10.1074/jbc.M308700200. PMID 12960149. 
  3. ^ Chen KG, Szakács G, Annereau JP, Rouzaud F, Liang XJ, Valencia JC, Nagineni CN, Hooks JJ, Hearing VJ, Gottesman MM (April 2005). "Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes". Pigment Cell Res. 18 (2): 102–12. doi:10.1111/j.1600-0749.2005.00214.x. PMID 15760339. 
  4. ^ Frank NY, Margaryan A, Huang Y, Schatton T, Waaga-Gasser AM, Gasser M, Sayegh MH, Sadee W, Frank MH (May 2005). "ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma". Cancer Res. 65 (10): 4320–33. doi:10.1158/0008-5472.CAN-04-3327. PMID 15899824. 
  5. ^ Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (January 2008). "Identification of cells initiating human melanomas". Nature 451 (7176): 345–9. doi:10.1038/nature06489. PMID 18202660. 
  6. ^ Ma J, Lin JY, Alloo A, Wilson BJ, Schatton T, Zhan Q, Murphy GF, Waaga-Gasser AM, Gasser M, Stephen Hodi F, Frank NY, Frank MH. (November 2010). "Isolation of tumorigenic circulating melanoma cells.". BBRC. 402 (4): 711–717. doi:10.1016/j.bbrc.2010.10.091. PMC 2998991. PMID 20977885. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2998991. 
  7. ^ Frank NY, Schatton T, Kim S, Zhan Q, Wilson BJ, Ma J, Saab KR, Osherov V, Widlund HR, Gasser M, Waaga-Gasser AM, Kupper TS, Murphy GF, Frank MH (January 2011). "VEGFR-1 expressed by malignant melanoma initiating cells is required for tumor growth". Cancer Res 71 (4): 1474–1485. doi:10.1158/0008-5472.CAN-10-1660. PMC 3083845. PMID 21212411. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3083845. 
  8. ^ Wilson BJ, Schatton T, Zhan Q, Gasser M, Ma J, Saab KR, Schanche R, Waaga-Gasser A, Gold JS, Huang Q, Murphy GF, Frank MH, Frank NY (June 2011). "ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients". Cancer Res.. doi:10.1158/0008-5472.CAN-11-0221. PMID 21652540. http://cancerres.aacrjournals.org/content/early/2011/06/06/0008-5472.CAN-11-0221.abstract. 

Further reading

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