Gene for Smelling Helps Cancer Cells Move to the Brain

From tasting a delicious meal to picking up pheromones, olfaction (or the sense of smell) involves a network of complex physiological pathways. Odor molecules latch on to olfactory receptors in the nose, and the signals are then shuttled off to the part of the brain where the information is processed. Interestingly, new research suggests that olfactory receptor genes may also be involved in a seemingly unrelated pathway: the metastasis of cancer cells from breast tumors to the brain.

A team of scientists from Massachusetts General Hospital has brought forward evidence that the olfactory receptor gene OR5B21 may be a prime target for future therapeutic approaches to limit the spread of malignant breast cells to the brain.

The WHO estimates that 2.3 million women worldwide were diagnosed with breast cancer (the world’s most prevalent cancer) in 2020. The cancer starts when breast cells such as the milk-producing ducts grow abnormally, dividing rapidly and accumulating to form a lump. These malignant cells can spread from the breast to the lymph nodes, where they circulate to other distant anatomical sites in a process known as metastasis.

Researchers have begun taking a closer look at olfactory receptor genes, given that these genes are highly overexpressed in prostate, lung, and liver cancers. However, they have yet to establish a clear link between these genes and breast cancer.

Here, the scientists used a genetically-engineered animal model of breast cancer to dissect the role of OR5B21 in breast cancer metastasis. They found that the gene is important during a process called epithelial to mesenchymal transition, or EMT. This process kicks off a cascade of phenotypic changes in cells, which accelerate their migration to distant organs such as the brain.

“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,” said the author’s senior author, Bakhos Tannous, adding that their work suggests that OR5B21 may figure prominently in breast cancer progression. 

Tannous says that the team hopes that using OR5B21 as a target for adjuvant cancer therapies could help extend the survival of breast cancer patients by blocking the movement of breast tumor cells to vital organs.