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Transcription factor PROX1: its role in development and cancer

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Abstract

The homeobox gene PROX1 is critical for organ development during embryogenesis. The Drosophila homologue, known as prospero has been shown to act as a tumor suppressor by controlling asymmetric cell division of neuroblasts. Likewise, alterations in PROX1 expression and function are associated with a number of human cancers including hematological malignancies, carcinomas of the pancreas, liver and the biliary system, sporadic breast cancer, Kaposiform hemangioendothelioma, colon cancer, and brain tumors. PROX1 is involved in cancer development and progression and has been ascribed both tumor suppressive and oncogenic properties in a variety of different cancer types. However, the exact mechanisms through which PROX1 regulates proliferation, migration, and invasion of cancer cells are by large unknown. This review provides an update on the role of PROX1 in organ development and on its emerging functions in cancer, with special emphasis on the central nervous system and glial brain tumors.

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References

  1. Abate-Shen, C. (2002). Deregulated homeobox gene expression in cancer: cause or consequence? Nature Reviews. Cancer, 2(10), 777–785.

    Article  PubMed  CAS  Google Scholar 

  2. Oliver, G., Sosa-Pineda, B., Geisendorf, S., Spana, E. P., Doe, C. Q., & Gruss, P. (1993). Prox1, a prospero-related homeobox gene expressed during mouse development. Mechanisms of Development, 44(1), 3–16.

    Article  PubMed  CAS  Google Scholar 

  3. Zinovieva, R. D., Duncan, M. K., Johnson, T. R., Torres, R., Polymeropoulos, M. H., & Tomarev, S. I. (1996). Structure and chromosomal localization of the human homeobox gene Prox1. Genomics, 35(3), 517–522.

    Article  PubMed  CAS  Google Scholar 

  4. Banerjee-Basu, S., Landsman, D., & Baxevanis, A. D. (1999). Threading analysis of prospero-type homeodomains. In Silico Biology, 1(3), 163–173.

    PubMed  CAS  Google Scholar 

  5. Ryter, J. M., Doe, C. Q., & Matthews, B. W. (2002). Structure of the DNA binding region of prospero reveals a novel homeo-prospero domain. Structure, 10(11), 1541–1549.

    Article  PubMed  CAS  Google Scholar 

  6. Yousef, M. S., & Matthews, B. W. (2005). Structural basis of prospero-DNA interaction: implications for transcription regulation in developing cells. Structure, 13(4), 601–607.

    Article  PubMed  CAS  Google Scholar 

  7. Song, K. H., Li, T., & Chiang, J. Y. (2006). A prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene. Journal of Biological Chemistry, 281(15), 10081–10088.

    Article  PubMed  CAS  Google Scholar 

  8. Steffensen, K. R., Holter, E., Bavner, A., Nilsson, M., Pelto-Huikko, M., Tomarev, S., et al. (2004). Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue. EMBO Reports, 5(6), 613–619.

    Article  PubMed  CAS  Google Scholar 

  9. Chen, X., Patel, T. P., Simirskii, V. I., & Duncan, M. K. (2008). PCNA interacts with Prox1 and represses its transcriptional activity. Molecular Vision, 14, 2076–2086.

    PubMed  CAS  Google Scholar 

  10. Pan, M. R., Chang, T. M., Chang, H. C., Su, J. L., Wang, H. W., & Hung, W. C. (2009). Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells. Journal of Cell Science, 122(Pt 18), 3358–3364.

    Article  PubMed  CAS  Google Scholar 

  11. Shan, S. F., Wang, L. F., Zhai, J. W., Qin, Y., Ouyang, H. F., Kong, Y. Y., et al. (2008). Modulation of transcriptional corepressor activity of prospero-related homeobox protein (Prox1) by SUMO modification. FEBS Letters, 582(27), 3723–3728.

    Article  PubMed  CAS  Google Scholar 

  12. Doe, C. Q., Chu-LaGraff, Q., Wright, D. M., & Scott, M. P. (1991). The prospero gene specifies cell fates in the Drosophila central nervous system. Cell, 65(3), 451–464.

    Article  PubMed  CAS  Google Scholar 

  13. Betschinger, J., & Knoblich, J. A. (2004). Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates. Current Biology, 14(16), R674–R685.

    Article  PubMed  CAS  Google Scholar 

  14. Jan, Y. N., & Jan, L. Y. (1998). Asymmetric cell division. Nature, 392(6678), 775–778.

    Article  PubMed  CAS  Google Scholar 

  15. Myster, D. L., & Duronio, R. J. (2000). To differentiate or not to differentiate? Current Biology, 10(8), R302–R304.

    Article  PubMed  CAS  Google Scholar 

  16. Betschinger, J., Mechtler, K., & Knoblich, J. A. (2006). Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell, 124(6), 1241–1253.

    Article  PubMed  CAS  Google Scholar 

  17. Knoblich, J. A. (2008). Mechanisms of asymmetric stem cell division. Cell, 132(4), 583–597.

    Article  PubMed  CAS  Google Scholar 

  18. Choksi, S. P., Southall, T. D., Bossing, T., Edoff, K., de Wit, E., Fischer, B. E., et al. (2006). Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Developmental Cell, 11(6), 775–789.

    Article  PubMed  CAS  Google Scholar 

  19. Hirata, J., Nakagoshi, H., Nabeshima, Y., & Matsuzaki, F. (1995). Asymmetric segregation of the homeodomain protein prospero during Drosophila development. Nature, 377(6550), 627–630.

    Article  PubMed  CAS  Google Scholar 

  20. Southall, T. D., & Brand, A. H. (2009). Neural stem cell transcriptional networks highlight genes essential for nervous system development. EMBO Journal, 28(24), 3799–3807.

    Article  PubMed  CAS  Google Scholar 

  21. Griffiths, R. L., & Hidalgo, A. (2004). Prospero maintains the mitotic potential of glial precursors enabling them to respond to neurons. EMBO Journal, 23(12), 2440–2450.

    Article  PubMed  CAS  Google Scholar 

  22. Raff, M. C., Durand, B., & Gao, F. B. (1998). Cell number control and timing in animal development: the oligodendrocyte cell lineage. International Journal of Developmental Biology, 42(3), 263–267.

    PubMed  CAS  Google Scholar 

  23. Stacey, S. M., Thomas, G. B., Labbe, A., & Van Meyel, D. J. (2007). Longitudinal glia in the fly CNS: pushing the envelope on glial diversity and neuron-glial interactions. Neuron Glia Biology, 3(1), 27–33.

    Article  PubMed  Google Scholar 

  24. Hidalgo, A., & Griffiths, R. (2004). Coupling glial numbers and axonal patterns. Cell Cycle, 3(9), 1118–1120.

    Article  PubMed  CAS  Google Scholar 

  25. Freeman, M. R., Delrow, J., Kim, J., Johnson, E., & Doe, C. Q. (2003). Unwrapping glial biology: gcm target genes regulating glial development, diversification, and function. Neuron, 38(4), 567–580.

    Article  PubMed  CAS  Google Scholar 

  26. Freeman, M. R., & Doe, C. Q. (2001). Asymmetric prospero localization is required to generate mixed neuronal/glial lineages in the Drosophila CNS. Development, 128(20), 4103–4112.

    PubMed  CAS  Google Scholar 

  27. Hong, Y. K., & Detmar, M. (2003). Prox1, master regulator of the lymphatic vasculature phenotype. Cell and Tissue Research, 314(1), 85–92.

    Article  PubMed  Google Scholar 

  28. Weller, M., & Tautz, D. (2003). Prospero and Snail expression during spider neurogenesis. Development Genes and Evolution, 213(11), 554–566.

    Article  PubMed  CAS  Google Scholar 

  29. Wigle, J. T., Chowdhury, K., Gruss, P., & Oliver, G. (1999). Prox1 function is crucial for mouse lens-fibre elongation. Nature Genetics, 21(3), 318–322.

    Article  PubMed  CAS  Google Scholar 

  30. Wigle, J. T., & Oliver, G. (1999). Prox1 function is required for the development of the murine lymphatic system. Cell, 98(6), 769–778.

    Article  PubMed  CAS  Google Scholar 

  31. Galeeva, A., Treuter, E., Tomarev, S., & Pelto-Huikko, M. (2007). A prospero-related homeobox gene Prox-1 is expressed during postnatal brain development as well as in the adult rodent brain. Neuroscience, 146(2), 604–616.

    Article  PubMed  CAS  Google Scholar 

  32. Lavado, A., & Oliver, G. (2007). Prox1 expression patterns in the developing and adult murine brain. Developmental Dynamics, 236(2), 518–524.

    Article  PubMed  CAS  Google Scholar 

  33. Kaltezioti, V., Kouroupi, G., Oikonomaki, M., Mantouvalou, E., Stergiopoulos, A., Charonis, A., et al. (2010). Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS Biology, 8(12), e1000565.

    Article  PubMed  CAS  Google Scholar 

  34. Karalay, O., Doberauer, K., Vadodaria, K. C., Knobloch, M., Berti, L., Miquelajauregui, A., et al. (2011). Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 108(14), 5807–5812.

    Article  PubMed  CAS  Google Scholar 

  35. Misra, K., Gui, H., & Matise, M. P. (2008). Prox1 regulates a transitory state for interneuron neurogenesis in the spinal cord. Developmental Dynamics, 237(2), 393–402.

    Article  PubMed  Google Scholar 

  36. Torii, M., Matsuzaki, F., Osumi, N., Kaibuchi, K., Nakamura, S., Casarosa, S., et al. (1999). Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system. Development, 126(3), 443–456.

    PubMed  CAS  Google Scholar 

  37. Elkouris, M., Balaskas, N., Poulou, M., Politis, P. K., Panayiotou, E., Malas, S., et al. (2011). Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis. Stem Cells. doi:10.1002/stem.554.

  38. Deng, W., Aimone, J. B., & Gage, F. H. (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nature Reviews Neuroscience, 11(5), 339–350.

    Article  PubMed  CAS  Google Scholar 

  39. Lavado, A., Lagutin, O. V., Chow, L. M., Baker, S. J., & Oliver, G. (2010). Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS Biology. doi:10.1371/1000460.

  40. Duncan, M. K., Cui, W., Oh, D. J., & Tomarev, S. I. (2002). Prox1 is differentially localized during lens development. Mechanisms of Development, 112(1–2), 195–198.

    Article  PubMed  CAS  Google Scholar 

  41. Tomarev, S. I., Sundin, O., Banerjee-Basu, S., Duncan, M. K., Yang, J. M., & Piatigorsky, J. (1996). Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina. Developmental Dynamics, 206(4), 354–367.

    Article  PubMed  CAS  Google Scholar 

  42. Dyer, M. A., Livesey, F. J., Cepko, C. L., & Oliver, G. (2003). Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nature Genetics, 34(1), 53–58.

    Article  PubMed  CAS  Google Scholar 

  43. Burke, Z., & Oliver, G. (2002). Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mechanisms of Development, 118(1–2), 147–155.

    Article  PubMed  CAS  Google Scholar 

  44. Sosa-Pineda, B., Wigle, J. T., & Oliver, G. (2000). Hepatocyte migration during liver development requires Prox1. Nature Genetics, 25(3), 254–255.

    Article  PubMed  CAS  Google Scholar 

  45. Dufour, C. R., Levasseur, M. P., Pham, N. H., Eichner, L. J., Wilson, B. J., Charest-Marcotte, A., et al. (2011). Genomic convergence among ERRalpha, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS Genetics, 7(6), e1002143.

    Article  PubMed  CAS  Google Scholar 

  46. Charest-Marcotte, A., Dufour, C. R., Wilson, B. J., Tremblay, A. M., Eichner, L. J., Arlow, D. H., et al. (2010). The homeobox protein Prox1 is a negative modulator of ERR{alpha}/PGC-1{alpha} bioenergetic functions. Genes & Development, 24(6), 537–542.

    Article  CAS  Google Scholar 

  47. Wang, J., Kilic, G., Aydin, M., Burke, Z., Oliver, G., & Sosa-Pineda, B. (2005). Prox1 activity controls pancreas morphogenesis and participates in the production of "secondary transition" pancreatic endocrine cells. Developmental Biology, 286(1), 182–194.

    Article  PubMed  CAS  Google Scholar 

  48. Wigle, J. T., Harvey, N., Detmar, M., Lagutina, I., Grosveld, G., Gunn, M. D., et al. (2002). An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO Journal, 21(7), 1505–1513.

    Article  PubMed  CAS  Google Scholar 

  49. Tammela, T., & Alitalo, K. (2010). Lymphangiogenesis: molecular mechanisms and future promise. Cell, 140(4), 460–476.

    Article  PubMed  CAS  Google Scholar 

  50. Johnson, N. C., Dillard, M. E., Baluk, P., McDonald, D. M., Harvey, N. L., Frase, S. L., et al. (2008). Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes & Development, 22(23), 3282–3291.

    Article  CAS  Google Scholar 

  51. Makinen, T., Norrmen, C., & Petrova, T. V. (2007). Molecular mechanisms of lymphatic vascular development. Cellular and Molecular Life Sciences, 64(15), 1915–1929.

    Article  PubMed  CAS  Google Scholar 

  52. Petrova, T. V., Makinen, T., Makela, T. P., Saarela, J., Virtanen, I., Ferrell, R. E., et al. (2002). Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO Journal, 21(17), 4593–4599.

    Article  PubMed  CAS  Google Scholar 

  53. Rodriguez-Niedenfuhr, M., Papoutsi, M., Christ, B., Nicolaides, K. H., von Kaisenberg, C. S., Tomarev, S. I., et al. (2001). Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts. Anat Embryol (Berl), 204(5), 399–406.

    Article  CAS  Google Scholar 

  54. Risebro, C. A., Searles, R. G., Melville, A. A., Ehler, E., Jina, N., Shah, S., et al. (2009). Prox1 maintains muscle structure and growth in the developing heart. Development, 136(3), 495–505.

    Article  PubMed  CAS  Google Scholar 

  55. Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., et al. (2007). The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica, 114(2), 97–109.

    Article  PubMed  Google Scholar 

  56. Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., et al. (2007). Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes & Development, 21(21), 2683–2710.

    Article  CAS  Google Scholar 

  57. Elsir, T., Eriksson, A., Orrego, A., Lindstrom, M. S., & Nister, M. (2010). Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas. Journal of Neuropathology and Experimental Neurology, 69(2), 129–138.

    Article  PubMed  CAS  Google Scholar 

  58. Elsir, T., Qu, M., Berntsson, S. G., Orrego, A., Olofsson, T., Lindstrom, M. S., et al. (2011). PROX1 is a predictor of survival for gliomas WHO grade II. British Journal of Cancer, 104(11), 1747–1754.

    Article  PubMed  CAS  Google Scholar 

  59. Holmberg, J., He, X., Peredo, I., Orrego, A., Hesselager, G., Ericsson, C., et al. (2011). Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma. PLoS One. doi:10.1371/journal.pone.0018454.

  60. Grau, S. J., Trillsch, F., von Luttichau, I., Nelson, P. J., Herms, J., Tonn, J. C., et al. (2008). Lymphatic phenotype of tumour vessels in malignant gliomas. Neuropathology and Applied Neurobiology, 34(6), 675–679.

    Article  PubMed  CAS  Google Scholar 

  61. Jenny, B., Harrison, J. A., Baetens, D., Tille, J. C., Burkhardt, K., Mottaz, H., et al. (2006). Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas. The Journal of Pathology, 209(1), 34–43.

    Article  PubMed  CAS  Google Scholar 

  62. Mueller, S., & Matthay, K. K. (2009). Neuroblastoma: biology and staging. Current Oncology Reports, 11(6), 431–438.

    Article  PubMed  Google Scholar 

  63. Becker, J., Wang, B., Pavlakovic, H., Buttler, K., & Wilting, J. (2010). Homeobox transcription factor Prox1 in sympathetic ganglia of vertebrate embryos: correlation with human stage 4 s neuroblastoma. Pediatric Research, 68(2), 112–117.

    Article  PubMed  CAS  Google Scholar 

  64. Kinzler, K. W., & Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell, 87(2), 159–170.

    Article  PubMed  CAS  Google Scholar 

  65. Petrova, T. V., Nykanen, A., Norrmen, C., Ivanov, K. I., Andersson, L. C., Haglund, C., et al. (2008). Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. Cancer Cell, 13(5), 407–419.

    Article  PubMed  CAS  Google Scholar 

  66. Edvardsson, K., Strom, A., Jonsson, P., Gustafsson, J. A., & Williams, C. (2011). Estrogen receptor beta induces antiinflammatory and antitumorigenic networks in colon cancer cells. Molecular Endocrinology, 25(6), 969–979.

    Article  PubMed  CAS  Google Scholar 

  67. Skog, M., Bono, P., Lundin, M., Lundin, J., Louhimo, J., Linder, N., et al. (2011). Expression and prognostic value of transcription factor PROX1 in colorectal cancer. British Journal of Cancer, 2011(4), 297.

    Google Scholar 

  68. Shimoda, M., Takahashi, M., Yoshimoto, T., Kono, T., Ikai, I., & Kubo, H. (2006). A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma. Clinical Cancer Research, 12(20 Pt 1), 6005–6011.

    Article  PubMed  CAS  Google Scholar 

  69. Akagami, M., Kawada, K., Kubo, H., Kawada, M., Takahashi, M., Kaganoi, J., et al. (2011). Transcriptional factor Prox1 plays an essential role in the antiproliferative action of interferon-gamma in esophageal cancer cells. Annals of Surgical Oncology, 18(13), 3868–3877.

    Article  PubMed  Google Scholar 

  70. Kaganoi, J., Watanabe, G., Okabe, M., Nagatani, S., Kawabe, A., Shimada, Y., et al. (2007). STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in vivo. Annals of Surgical Oncology, 14(4), 1405–1415.

    Article  PubMed  Google Scholar 

  71. Schneider, M., Buchler, P., Giese, N., Giese, T., Wilting, J., Buchler, M. W., et al. (2006). Role of lymphangiogenesis and lymphangiogenic factors during pancreatic cancer progression and lymphatic spread. International Journal of Oncology, 28(4), 883–890.

    PubMed  CAS  Google Scholar 

  72. Laerm, A., Helmbold, P., Goldberg, M., Dammann, R., Holzhausen, H. J., & Ballhausen, W. G. (2007). Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system. Journal of Hepatology, 46(1), 89–97.

    Article  PubMed  CAS  Google Scholar 

  73. Nagai, H., Li, Y., Hatano, S., Toshihito, O., Yuge, M., Ito, E., et al. (2003). Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies. Genes, Chromosomes & Cancer, 38(1), 13–21.

    Article  CAS  Google Scholar 

  74. Versmold, B., Felsberg, J., Mikeska, T., Ehrentraut, D., Kohler, J., Hampl, J. A., et al. (2007). Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer. International Journal of Cancer, 121(3), 547–554.

    Article  CAS  Google Scholar 

  75. Uldrick, T. S., & Whitby, D. (2011). Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment of Kaposi Sarcoma. Cancer Letters, 305(2), 150–162.

    Article  PubMed  CAS  Google Scholar 

  76. Jussila, L., Valtola, R., Partanen, T. A., Salven, P., Heikkila, P., Matikainen, M. T., et al. (1998). Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Research, 58(8), 1599–1604.

    PubMed  CAS  Google Scholar 

  77. Hong, Y. K., Foreman, K., Shin, J. W., Hirakawa, S., Curry, C. L., Sage, D. R., et al. (2004). Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nature Genetics, 36(7), 683–685.

    Article  PubMed  CAS  Google Scholar 

  78. Yoo, J., Kang, J., Lee, H. N., Aguilar, B., Kafka, D., Lee, S., et al. (2010). Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi's sarcoma herpes virus. PLoS Pathogens, 6(8), e1001046.

    Article  PubMed  Google Scholar 

  79. Elyada, E., Pribluda, A., Goldstein, R. E., Morgenstern, Y., Brachya, G., Cojocaru, G., et al. (2011). CKIalpha ablation highlights a critical role for p53 in invasiveness control. Nature, 470(7334), 409–413.

    Article  PubMed  CAS  Google Scholar 

  80. Dadras, S. S., Skrzypek, A., Nguyen, L., Shin, J. W., Schulz, M. M., Arbiser, J., et al. (2008). Prox-1 promotes invasion of kaposiform hemangioendotheliomas. The Journal of Investigative Dermatology, 128(12), 2798–2806.

    Article  PubMed  CAS  Google Scholar 

  81. Cao, Y. (2005). Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nature Reviews. Cancer, 5(9), 735–743.

    Article  PubMed  CAS  Google Scholar 

  82. Duong, T., Koopman, P., & Francois, M. (2012). Tumor lymphangiogenesis as a potential therapeutic target. J Oncol. doi:10.1155/2012/204946.

  83. Hope, K. J., Cellot, S., Ting, S. B., MacRae, T., Mayotte, N., Iscove, N. N., et al. (2010). An RNAi screen identifies Msi2 and Prox1 as having opposite roles in the regulation of hematopoietic stem cell activity. Cell Stem Cell, 7(1), 101–113.

    Article  PubMed  CAS  Google Scholar 

  84. Monzani, E., Facchetti, F., Galmozzi, E., Corsini, E., Benetti, A., Cavazzin, C., et al. (2007). Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. European Journal of Cancer, 43(5), 935–946.

    Article  PubMed  CAS  Google Scholar 

  85. Balla, M. M., Vemuganti, G. K., Kannabiran, C., Honavar, S. G., & Murthy, R. (2009). Phenotypic characterization of retinoblastoma for the presence of putative cancer stem-like cell markers by flow cytometry. Investigative Ophthalmology & Visual Science, 50(4), 1506–1514.

    Article  Google Scholar 

  86. Steiner, B., Zurborg, S., Horster, H., Fabel, K., & Kempermann, G. (2008). Differential 24 h responsiveness of Prox1-expressing precursor cells in adult hippocampal neurogenesis to physical activity, environmental enrichment, and kainic acid-induced seizures. Neuroscience, 154(2), 521–529.

    Article  PubMed  CAS  Google Scholar 

  87. Zheng, H., Ying, H., Yan, H., Kimmelman, A. C., Hiller, D. J., Chen, A. J., et al. (2008). Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harbor Symposia on Quantitative Biology, 73, 427–437.

    Article  PubMed  CAS  Google Scholar 

  88. Srinivasan, R. S., Geng, X., Yang, Y., Wang, Y., Mukatira, S., Studer, M., et al. (2010). The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells. Genes & Development, 24(7), 696–707.

    Article  CAS  Google Scholar 

  89. Yoshimatsu, Y., Yamazaki, T., Mihira, H., Itoh, T., Suehiro, J., Yuki, K., et al. (2011). Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1. Journal of Cell Science, 124(Pt 16), 2753–2762.

    Article  PubMed  CAS  Google Scholar 

  90. Azuma, K., Urano, T., Watabe, T., Ouchi, Y., & Inoue, S. (2011). PROX1 suppresses vitamin K-induced transcriptional activity of steroid and xenobiotic receptor. Genes to Cells, 16(11), 1063–1070.

    Article  PubMed  CAS  Google Scholar 

  91. Takahashi, M., Yoshimoto, T., Shimoda, M., Kono, T., Koizumi, M., Yazumi, S., et al. (2006). Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human cancer cells. Neoplasia, 8(12), 1003–1010.

    Article  PubMed  CAS  Google Scholar 

  92. Dudas, J., Mansuroglu, T., Moriconi, F., Haller, F., Wilting, J., Lorf, T., et al. (2008). Altered regulation of Prox1-gene-expression in liver tumors. BMC Cancer, 8(92), 92.

    Article  PubMed  Google Scholar 

  93. Yoshimoto, T., Takahashi, M., Nagayama, S., Watanabe, G., Shimada, Y., Sakasi, Y., et al. (2007). RNA mutations of prox1 detected in human esophageal cancer cells by the shifted termination assay. Biochemical and Biophysical Research Communications, 359(2), 258–262.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work has been supported by funds from the King Gustav V Jubilee Fund, Stockholm (MN and AS), the Swedish Cancer Society (MN), and the Swedish Research Council (MN), including the VR-Linné (STARGET) fund. TE is currently supported by a postdoc stipendium from the Medical Faculty, Uppsala University.

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The authors declare no conflict of interest related to this work.

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Elsir, T., Smits, A., Lindström, M.S. et al. Transcription factor PROX1: its role in development and cancer. Cancer Metastasis Rev 31, 793–805 (2012). https://doi.org/10.1007/s10555-012-9390-8

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