AACR 2021: Role of ROBO1 Receptor in Growth of Multiple Myeloma
Posted: Tuesday, April 27, 2021
The transmembrane receptor Roundabout 1 (ROBO1) has been found to play a role in the growth and dissemination of solid tumors; however, its function in patients with multiple myeloma is unknown. Giada Bianchi, MD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues conducted a study to identify novel signaling pathways supporting multiple myeloma pathogenesis. Their findings, which were presented during the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract LB217), suggested the ROBO1 C-terminus may be a novel molecular target in this disease.
“We show for the first time that ROBO1 is necessary for multiple myeloma growth and homing to the bone marrow,” the investigators commented. “Cleaved ROBO1 cytosolic domain translocates to the nucleus and is necessary and sufficient to rescue ROBO1 knockout proliferative defect, possibly by participating in RNA processing.”
The investigators conducted in vivo experiments using mice and several laboratory assessments to analyze the biologic mechanisms associated with ROBO1 expression. Protein structure and function studies revealed that ROBO1 expression might be necessary for the adhesion of multiple myeloma to the bone marrow stromal and endothelial cells; in a disseminated mouse model, ROBO1 knockout seemed to compromise bone marrow homing and engraftment. Compared with the wild-type, ROBO1 knockout appeared to significantly decrease intramedullary (P = .02) and extramedullary (P = .001) tumor growth in vivo; multiple myeloma proliferation also seemed to decrease in vitro significantly.
According to the investigators, the ROBO1 C-terminus is cleaved in a ligand-independent fashion, promoting multiple myeloma proliferation. Mutants lacking the cytoplasmic domain seemed to act dominantly negative. Further research is needed to determine the function of ROBO1 in RNA processing.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.