Olfactory receptor 5B21 drives breast cancer metastasis
Mao Li,
Markus W. Schweiger,
Daniel J. Ryan,
Ichiro Nakano,
Litia A. Carvalho,
Bakhos A. Tannous
Affiliations
Mao Li
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA
Markus W. Schweiger
Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Department of Neurosurgery, Cancer Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, the Netherlands
Daniel J. Ryan
Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA
Ichiro Nakano
Department of Neurosurgery and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Litia A. Carvalho
Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Corresponding author
Bakhos A. Tannous
Experimental Therapeutics and Molecular Imaging Laboratory, Department of Neurology, Neuro-Oncology Division, Massachusetts General Hospital, 149 13th Street, Charlestown, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Corresponding author
Summary: Olfactory receptors (ORs), responsible for the sense of smell, play an essential role in various physiological processes outside the nasal epithelium, including cancer. In breast cancer, however, the expression and function of ORs remain understudied. We examined the significance of OR transcript abundance in primary and metastatic breast cancer to the brain, bone, and lung. Although 20 OR transcripts were differentially expressed in distant metastases, OR5B21 displayed an increased transcript abundance in all three metastatic sites compared with the primary tumor. Knockdown of OR5B21 significantly decreased the invasion and migration of breast cancer cells as well as metastasis to different organs especially the brain, whereas increasing of OR5B21 transcript abundance had the opposite effect. Mechanistically, OR5B21 expression was associated with epithelial to mesenchymal transition through the STAT3/NF-κB/CEBPβ signaling axis. We propose OR5B21 (and potentially other ORs) as a novel oncogene contributing to breast cancer metastasis and a potential target for adjuvant therapy.
