Definition
RANKL is a member of the tumor necrosis factor (TNF) superfamily of cytokinesthat binds to its cognate receptor RANK. RANKL is a type II transmembrane glycoprotein of 317 amino acids which exists either in a membrane-bound form (40–45 kDa) or a soluble form (31 kDa) and is expressed with highest levels in skeletal and lymphoid tissues and to a lower extent in the heart, skeletal muscle, lung, stomach, placenta, and thyroid gland. RANK encodes a type I transmembrane glycoprotein of 616 amino acids (80–96 kDa) and is expressed in the skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, and pancreas. Signaling through RANK provides the essential signal for osteoclast differentiation, activation, and survival. Moreover, genetically...
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References
Asagiri M, Takayanagi H (2007) The molecular understanding of osteoclast differentiation. Bone 40(2):251–264
Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, Morony S, Rubin E, Sarao R, Hojilla CV, Komnenovic V, Kong YY, Schreiber M, Dixon SJ, Sims SM, Khokha R, Wada T, Penninger JM (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440(7084):692–696
Kong YY, Yoshida H, Sarosi I et al (1999) OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–323
Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593
Schramek D, Leibbrandt A, Sigl V, Kenner L, Pospisilik JA, Lee HJ, Hanada R, Joshi PA, Aliprantis A, Glimcher L, Pasparakis M, Khokha R, Ormandy CJ, Widschwendter M, Schett G, Penninger JM (2010) Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468(7320):98–102. doi:10.1038/nature09387. Epub 2010 Sep 29. PMID: 20881962 Free PMC Article
Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, Van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379(9810):39–46. doi:10.1016/S0140-6736(11)61226-9. Epub 2011 Nov
Theill LE, Boyle WJ, Penninger JM (2002) RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol 20:795–823
Walsh MC, Kim N, Kadono Y (2006) Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 24:33–63
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Leibbrandt, A., Penninger, J.M. (2015). RANK–RANKL Signaling. In: Schwab, M. (eds) Encyclopedia of Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27841-9_4945-2
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DOI: https://doi.org/10.1007/978-3-642-27841-9_4945-2
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