ABSTRACT
[ ABSTRACT] Chemokines and their receptors have been implicated mostly in tumor progression and metastasis. Atypical chemokine receptors ( ACKRs) comprise a group of 7-transmembrane domain proteins structurally similar to G pro-tein-coupled receptors.However, ACKRs do not induce classical signaling via the typical G protein-mediated pathways. ACKRs efficiently internalize the cognate chemokine ligands and act as scavengers instead.ACJRs are composed of at least 3 members of chemokine receptors: Duffy antigen receptor for chemokines ( DARC, also known as ACKR1 ) , D6 ( also known as ACKR2) and ChemoCentryx chemokine receptor (CCX-CKR, also known as ACKR4).These receptors bind to and/or internalize their chemoattractant ligands without activating signal transduction cascades leading to cell migration.In this review, we summarize the recent progress regarding the roles of ACKRs in the progression and metastasis of tumor.
ABSTRACT
Many chemokines and chemokine receptors, such as CCL2 and CXCR4, participate in the growth, angiogenesis, distal metastasis of breast cancer. However, the recent failures in the clinical trials of some single target antagonists suggest that chemokine network in tumor microenvironment is really complicated. Obviously, multi-targets regulation strategy for chemokines is indispensable based on the polypharmacological principle in the future. Atypical chemokine receptors (ACR) as endogenous and physiological regulators, including Duffy antigen receptor for chemokines (DARC), D6 and ChemoCentryx chemokine receptor (CCX-CKR), may be the powerful candidates for this purpose.