Unexpected functionality of an atypical chemokine receptor opens new avenues for cancer therapy
In a recent publication in Nature Communications, researchers from the Receptor Biochemistry Signaling group in the Department of Chemistry and Pharmaceutical Sciences, together with partners from the MSCA ITN network ONCORNET2.0, uncovered a novel role for ACKR3, a constitutively active atypical chemokine receptor highly expressed in cancer. Their work demonstrated that ACKR3's basal activity unexpectedly influences oncogenic cell motility. Using advanced structural dynamics approaches, they demonstrated that several ACKR3-targeting nanobodies, single-domain antibodies, act as inverse agonists and effectively stabilise inactive receptor conformations. These nanobodies suppress basal cell motility, thereby revealing a distinct and previously undescribed functional role for ACKR3 in cellular and cancer biology. These findings not only deepen our understanding of atypical chemokine receptor function but also open new therapeutic avenues for targeting ACKR3 in oncology and beyond.