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Olfactory Receptor Gene Has Important Role In Breast Cancer Metastasis

Researchers at the Massachusetts General Hospital have discovered that an olfactory receptor gene, which is important in the sense of smell, has an important role to play in the metastasis of breast cancer to the brain, bones and lung. The research team also found that constraining the gene, known as OR5B21, drastically reduced the metastasis of breast cancer cells to these organs. This discovery could prove to be important for future course of treatment to stop the spread of cancer to different parts of the body.

Commenting on the findings, Bakhos Tannous, director of the Experimental Therapeutics Unit in the Department of Neurology at MGH and senior author of the study, said, "The common perception is that the only role of olfactory receptors, which line the nasal cavity and relay sensory data to the brain, is to recognize odor and smell. Our work suggests that the olfactory receptor 5B21 is also a novel oncogene that may figure prominently in cancer progression by driving breast cancer cells to the brain and other sites in the body."

Breast cancer is the second-most frequently diagnosed malignancy after lung cancer, and the leading cause of cancer in women, with more than two million new cases being reported each year. Moreover, migration of breast cancer to the brain is the leading cause of mortality from the disease, thus making it important to find treatment to delay or halt its metastasis.

As part of their research, the team conducted experiments on animal models and found that OR5B21 enhances breast cancer cells to metastasize through a signaling pathway, which activates a process known as the epithelial to mesenchymal transition or EMT. EMT prompts multiple biochemical or phenotypical changes in the olfactory cells which include enhanced migratory capacity to distant organs, especially the brain.

Lead author Mao Li said, "This activation converts a wide range of extracellular signals into intracellular messages through the signaling pathway NF-?B/STAT, resulting in cell proliferation, invasion and metastasis. Our findings are novel for the field, though further research is needed to determine exactly how OR5B21 induces metastasis."

The team is of the opinion that future research might also lead to a molecular inhibitor of OR5B21 in response to the discovery that downregulating the olfactory receptor led to a major decrease in the breast cancer cell metastasis.

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