ABCB5
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][5]
ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in human malignant melanoma. It is commonly over-expressed on circulating melanoma tumour cells.[6][7] 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.[8]
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.[9] These data revealed multiple roles for ABCB5 in cancer progression and chemoresistance, making it an attractive target for combined therapy. ABCB5 was similarly demonstrated in melanoma to be functionally important to multi-drug chemotherapy resistance, and tumor growth, controlling a proinflammatory signaling circuit utilizing TLR4, IL-1β, IL8 and CXCR1 signaling involving reciprocal paracrine interactions between the melanoma stem cell and tumor bulk population (in a rheostat manner termed "cancer stem cell rheostasis" by the authors). ABCB5 was shown to maintain the slow-cycling melanoma stem cells using this cytokine signaling loop, which became more differentiated upon ABCB5 interference (e.g. WFDC1 melanocyte differentiation marker increased, cancer cells were faster growing in vitro, tumors were more pigmented), or CXCR1 blockade (slow-cycling ABCB5+ cells entered the cell-cycle).[10]
In normal physiology ABCB5 was shown to be a functional marker for adult limbal stem cells of the cornea; ABCB5+ cells could regrow a human cornea on a mouse with limbal stem cell deficiency (LSCD - a blindness disease of the corneal limbus) while ABCB5- cells could not, indicating a therapeutic potential for treating some types of blindness. ABCB5 was further shown to be anti-apoptotic in these adult stem cells.[11]
References
- ↑ 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.
- ↑ 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.
- ↑ 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 (ABCB5 alpha and ABCB5 beta ) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes". Pigment Cell Res. 18 (2): 102–12. doi:10.1111/j.1600-0749.2005.00214.x. PMID 15760339.
- ↑ 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.
- ↑ Chen KG, Valencia JC, Gillet JP, Hearing VJ, Gottesman MM (Dec 2009). "Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma". Pigment Cell Melanoma Res. 22 (6): 740–9. doi:10.1111/j.1755-148X.2009.00630.x. PMC 2766009. PMID 19725928.
- ↑ 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. PMC 3660705. PMID 18202660.
- ↑ 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.
- ↑ 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.
- ↑ 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. 71 (15): 5307–16. doi:10.1158/0008-5472.CAN-11-0221. PMC 3395026. PMID 21652540.
- ↑ Wilson BJ, Saab KR, Ma J, Schatton T, Putz P, Zhan Q, Murphy GF, Gasser M, Waaga-Gasser AM, Frank NY, Frank MH (Aug 2014). "ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit.". Cancer Res 74 (15): 4196–4207. doi:10.1158/0008-5472.CAN-14-0582. PMID 24934811.
- ↑ Ksander BR, Kolovou PE, Wilson BJ, Saab KR, Guo Q, Ma J, McGuire SP, Gregory MS, Vincent WJ, Perez VL, Cruz-Guilloty F, Kao WW, Call MK, Tucker BA, Zhan Q, Murphy GF, Lathrop KL, Alt C, Mortensen LJ, Lin CP, Zieske JD, Frank MH, Frank NY (July 2014). "ABCB5 is a limbal stem cell gene required for corneal development and repair.". Nature 511 (7509): 353–357. doi:10.1038/nature13426. PMID 25030174.
Further reading
- Chen KG, Valencia JC, Gillet JP, Hearing VJ, Gottesman MM (2009). "Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma". Pigment Cell Melanoma Res. 22 (6): 740–9. doi:10.1111/j.1755-148X.2009.00630.x. PMC 2766009. PMID 19725928.
- Corrocher R, Tedesco F, Rabusin P, De Sandre G (1975). "Effect of human erythrocyte stromata on complement activation". Br. J. Haematol. 29 (2): 235–41. doi:10.1111/j.1365-2141.1975.tb01817.x. PMID 33.
- Scherer SW, Cheung J, MacDonald JR; et al. (2003). "Human chromosome 7: DNA sequence and biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Frank NY, Frank MH (2009). "ABCB5 gene amplification in human leukemia cells". Leuk. Res. 33 (10): 1303–5. doi:10.1016/j.leukres.2009.04.035. PMC 2760090. PMID 19477512.
- Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Chen KG, Szakacs G, Annereau JP; et al. (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.
- Huang Y, Anderle P, Bussey KJ; et al. (2004). "Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance". Cancer Res. 64 (12): 4294–301. doi:10.1158/0008-5472.CAN-03-3884. PMID 15205344.
- Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H.; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Malorni W, Lucia MB, Rainaldi G; et al. (1998). "Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients". Haematologica 83 (1): 13–20. PMID 9542318.
- Matalon ST, Drucker L, Fishman A; et al. (2008). "The Role of heat shock protein 27 in extravillous trophoblast differentiation". J. Cell. Biochem. 103 (3): 719–29. doi:10.1002/jcb.21476. PMID 17661346.
- Begley GS, Horvath AR, Taylor JC, Higgins CF (2005). "Cytoplasmic domains of the transporter associated with antigen processing and P-glycoprotein interact with subunits of the proteasome". Mol. Immunol. 42 (1): 137–41. doi:10.1016/j.molimm.2004.07.005. PMID 15488952.
- Glessner JT, Bradfield JP, Wang K, Takahashi N, Zhang H, Sleiman PM, Mentch FD, Kim CE, Hou C, Thomas KA, Garris ML, Deliard S, Frackelton EC, Otieno FG, Zhao J, Chiavacci RM, Li M, Buxbaum JD, Berkowitz RI, Hakonarson H, Grant SF (2010). "A Genome-wide Study Reveals Copy Number Variants Exclusive to Childhood Obesity Cases". American Journal of Human Genetics 87 (5): 661–6. doi:10.1016/j.ajhg.2010.09.014. PMC 2978976. PMID 20950786.
- Fukunaga-Kalabis M, Martinez G, Nguyen TK, Kim D, Santiago-Walker A, Roesch A, Herlyn M. (2010). "Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population". Oncogene 29 (46): 6115–24. doi:10.1038/onc.2010.350+l. PMC 2991494. PMID 20729912.
- Cheung ST, Cheung PF, Cheng CK, Wong NC, Fan ST. (2010). "Granulin-Epithelin Precursor and ATP-Dependent Binding Cassette (ABC)B5 Regulate Liver Cancer Cell Chemoresistance". Gastroenterology 140 (1): 344–55. doi:10.1053/j.gastro.2010.07.049. PMID 20682318.
- Yang JY, Ha SA, Yang YS, Kim JW. (2010). "p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance". BMC Cancer 10: 388. doi:10.1186/1471-2407-10-388. PMC 2913965. PMID 20649952.
- Sharma BK, Manglik V, Elias EG. (2010). "Immuno-expression of human melanoma stem cell markers in tissues at different stages of the disease". J Surg Res. 163 (1): e11–5. doi:10.1016/j.jss.2010.03.043. PMID 20638684.
- Gazzaniga P, Cigna E, Panasiti V, Devirgiliis V, Bottoni U, Vincenzi B, Nicolazzo C, Petracca A, Gradilone A. (2010). "CD133 and ABCB5 as stem cell markers on sentinel lymph node from melanoma patients". Eur J Surg Oncol. 36 (12): 1211–4. doi:10.1016/j.ejso.2010.05.001. PMID 20573479.
- Ma J, Frank MH. (2010). "Tumor initiation in human malignant melanoma and potential cancer therapies". Anticancer Agents Med Chem. 10 (2): 131–6. doi:10.2174/187152010790909254. PMC 2885608. PMID 20184545.
- Schatton T, Schütte U, Frank NY, Zhan Q, Hoerning A, Robles SC, Zhou J, Hodi FS, Spagnoli GC, Murphy GF, Frank MH. (2010). "Modulation of T-cell activation by malignant melanoma initiating cells". Cancer Res. 70 (2): 697–708. doi:10.1158/0008-5472.CAN-09-1592. PMC 2883769. PMID 20068175.
External links
- ABCB5 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- ABCB5 human gene location in the UCSC Genome Browser.
- ABCB5 human gene details in the UCSC Genome Browser.
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