Researchers from Massachusetts General Hospital (MGH) have found that an olfactory receptor gene that aids in an individual’s sense of smell may also play a role in the metastasis of breast cancer.
Breast cancer is the second most commonly diagnosed malignancy. It is also the leading cause of cancer death in women, resulting in more than 2 million new cases each year. Standard therapy consists of surgery followed by radiation and chemotherapy. Although this has decreased cancer mortality, around 12% of patients are still at high risk of relapse. Most importantly, breast cancer metastasis, particularly to the brain, is one of the major causes of mortality. As a result, the identification of novel therapeutic targets to prevent or delay metastasis is critical.
The human olfactory receptor family is a crucial member of G-protein coupled receptors (GPCRs) that are typically expressed in sensory neurons. This family is known to be overexpressed in a variety of cancers, including prostate, melanoma, lung and liver. However, its role in breast cancer has previously been understudied.
The role of an olfactory receptor in metastasis
In a recent study, published in iScience, researchers evaluated the expression profiles of olfactory receptors in primary and metastatic breast cancer sites. These sites included the brain, bone and lung.
The team found 20 differentially expressed olfactory receptors. Among these, OR5B21 was upregulated in all organ metastases, with the highest being the brain.
Using animal models, the team found that knockdown of OR5DB21 significantly decreased the invasion and migration of breast cancer cells. It also reduced metastasis to different organs especially the brain. In comparison, increasing the transcript abundance of OR5B21 had the opposite effect. The team learned that OR5B21 expression was associated with epithelial to mesenchymal transition (EMT) through the STAT3/NF-κB/CEBPβ signalling axis. EMT facilitates various changes in olfactory cells, including enhanced migratory capacity to distant organs.
Overall, this study provides evidence for OR5B21 as a novel oncogene that contributes to breast cancer metastasis. While further research is needed to determine exactly how OR5B21 induces metastasis, this receptor represents a potential new target for breast cancer.
Bakhos Tannous, senior author, stated:
“Our hope is that using OR5B21 as a target for adjuvant therapy could help fill a huge unmet medical need by preventing breast cancer metastasis to the brain and other organs, and thus prolong survival of patients.”
Image credit: canva