Atypical chemokine receptors in tumor cell growth and metastasis

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Atypical chemokine receptors (ACKRs) are seven-transmembrane cell surface protein receptors expressed in immune cells, normal mesenchymal cells, and several tumor cells. As of this writing, six ACKRs have been characterized by diverse activities. They bind both cysteine-cysteine (CC) type and cysteine-X-cysteine (CXC)-type chemokines, either alone, or together with a ligand bound-functional G-protein coupled (typical) chemokine receptor. The major structural difference between ACKRs and typical chemokine receptors is the substituted DRYLAIV amino acid motif in the second intracellular loop of the ACKR. Due to this substitution, these receptors cannot bind Gαi-type G-proteins responsible for intracellular calcium mobilization and cellular chemotaxis. Although initially characterized as non-signaling transmembrane receptors (decoy receptors) that attenuate ligand-induced signaling by GPCRs, studies of all ACKRs have shown ligand-independent and ligand-dependent transmembrane signaling in both non-tumor and tumor cells. The precise function and mechanism of the differential expression of ACKRs in many tumors are not understood well. The use of antagonists of ACKRs ligands has shown limited antitumor potential; however, depleting ACKR expression resulted in a reduction in experimental tumor growth and metastasis. The ACKRs represent a unique class of transmembrane signaling proteins that regulate growth, survival, and metastatic processes in tumor cells, affecting multiple pathways of tumor growth. Therefore, closer investigations of ACKRs have a high potential for identifying therapeutics which affect the intracellular signaling, preferentially via the ligand-independent mechanism.

Original languageEnglish (US)
Title of host publicationAdvances in Cancer Research
PublisherAcademic Press Inc.
Pages1-27
Number of pages27
DOIs
StatePublished - 2020

Publication series

NameAdvances in Cancer Research
Volume145
ISSN (Print)0065-230X
ISSN (Electronic)2162-5557

Keywords

  • Alternate growth signaling
  • Cancer metastasis
  • Chemokines and chemokine receptors
  • Epidermal growth factor receptor
  • G-protein coupled receptors
  • Stromal derived growth factors
  • β-Arrestin-1 and 2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Lokeshwar, B. L., Kallifatidis, G., & Hoy, J. J. (2020). Atypical chemokine receptors in tumor cell growth and metastasis. In Advances in Cancer Research (pp. 1-27). (Advances in Cancer Research; Vol. 145). Academic Press Inc.. https://doi.org/10.1016/bs.acr.2019.12.002