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The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer

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Tumor Microenvironment

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1277))

Abstract

RANK ligand (RANKL) is a member of the tumor necrosis factor alpha superfamily of cytokines. It is the only known ligand binding to a membrane receptor named receptor activator of nuclear factor-kappa B (RANK), thereby triggering recruitment of TNF receptor-associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor, osteoprotegerin (OPG), but also has additional more complex levels of regulation. It is crucial for the differentiation of bone-resorbing osteoclasts and is deregulated in disease processes such as osteoporosis and cancer bone metastasis. Cells expressing RANK and RANKL are commonly found in the tumor environment. In many tumor types, the RANK/RANKL pathway is overexpressed, and this is in most cases correlated with poor prognosis. RANK signaling plays an important role in the innate and adaptive immune response, generates regulatory T (Treg) cells, and increases the production of cytokines. It is also involved in chemo resistance in vitro. Recent evidence suggests that RANKL blockade improves the efficacy of anti-CTLA-4 antibodies against solid tumors and experimental metastasis. Therefore, there is increasing interest to use RANKL inhibition as an immunomodulatory strategy in an attempt to make immune-resistant tumor responsive to immune therapy.

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Authors and Affiliations

  1. Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium

    Peter A. van Dam, Yannick Verhoeven & Xuan B. Trinh

  2. Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium

    Peter A. van Dam, Yannick Verhoeven & Xuan B. Trinh

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Correspondence to Peter A. van Dam .

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  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Alexander Birbrair

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van Dam, P.A., Verhoeven, Y., Trinh, X.B. (2020). The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer. In: Birbrair, A. (eds) Tumor Microenvironment . Advances in Experimental Medicine and Biology, vol 1277. Springer, Cham. https://doi.org/10.1007/978-3-030-50224-9_3

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