Exploiting agonist biased signaling of chemokines to target cancer. Mol Carcinog 2017 Mar;56(3):804-813
Date
09/21/2016Pubmed ID
27648825Pubmed Central ID
PMC5479419DOI
10.1002/mc.22571Scopus ID
2-s2.0-84994851814 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
As knowledge of growth-independent functions of cancer cells is expanding, exploration into the role of chemokines in modulating cancer pathogenesis, particularly metastasis, continues to develop. However, more study into the mechanisms whereby chemokines direct the migration of cancer cells is needed before specific therapies can be generated to target metastasis. Herein, we draw attention to the longstanding conundrum in the field of chemokine biology that chemokines stimulate migration in a biphasic manner; and explore this phenomenon's impact on chemokine function in the context of cancer. Typically, low concentrations of chemokines lead to chemotactic migration and higher concentrations halt migration. The signaling mechanisms that govern this phenomenon remain unclear. Over the last decade, we have defined a novel signaling mechanism for regulation of chemokine migration through ligand oligomerization and biased agonist signaling. We provide insight into this new paradigm for chemokine signaling and discuss how it will impact future exploration into chemokine function and biology. In the pursuit of producing more novel cancer therapies, we suggest a framework for pharmaceutical application of the principles of chemokine oligomerization and biased agonist signaling in cancer. © 2016 Wiley Periodicals, Inc.
Author List
Roy I, Getschman AE, Volkman BF, Dwinell MBAuthors
Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Cell Movement
Chemokines
Disease Progression
Humans
Models, Molecular
Neoplasms
Protein Multimerization
Receptors, G-Protein-Coupled
Signal Transduction
