Fatty acid binding protein found to have significant role in prostate cancer metastasis

University of Alberta researchers have discovered a protein that potentially could be targeted to help treat prostate cancer. In a new study, the team found an association between increased levels of fatty acid binding protein 12 (FABP12) and aggressive properties in prostate cancer.

If prostate cancer is caught in the early stages, patients have a more favourable prognosis. However, patient survival drops dramatically when the cancer has spread beyond the prostate. The researchers say understanding the mechanisms behind prostate cancer metastasis is crucial to improving patient outcomes.

“Metastasis is a complex process involving lots of changes in the cell, and one thing that’s really important is the cells’ energy needs,” says Rongzong Liu, research associate in the Department of Oncology. “Prostate cancer cells, unlike other cancers, use lipids rather than glucose for energy production. They prefer fatty acids to provide energy for the cells to metastasize.” 

Fatty acids are lipids that require a “chaperone”—fatty acid binding proteins—to move from one part of the cell to another. The team identified that the FABP12 gene can be found in higher levels within patients that have metastatic prostate cancer, and hypothesized that the abundance of FABP12 in this particular patient population could indicate it had an important role in metastasis.

Looking for a mechanism, they discovered that FABP12 activates a cell nuclear receptor called PPARγ. PPARs play a crucial role in regulating cancer cells and tumour growth, and PPARγ in particular has previously been reported as a driver of metastasis in prostate cancer, as it is linked to fatty acid signalling and lipid metabolism in the body. 

Liu and his team further determined that FABP12 and PPARγ form a pathway that causes epithelial-to-mesenchymal transition (EMT), a process that makes cells more mobile and invasive, and causes the cells to become more reliant on fatty acids for fuel. A mobile and aggressive cell is a cell that metastasizes—and this particular pathway appears to be a crucial piece of the puzzle in understanding how to control prostate cancer metastasis.

Next steps involve looking at how FABP12 may be involved in treatment resistance and how to disrupt this metastasis-driving pathway. While there are inhibitors available that target fatty acid binding proteins more generally, Liu is hoping to refine that into an inhibitor specifically designed to target FABP12. “We're thinking that if we block this pathway, target FABP12, it may stop metastasis for patients who express high levels of FABP12,” says Liu.

The researchers who worked on the study include Deepak Dinakaran and Ron Moore (Department of Surgery), Helene Lemieux and her student Woo Hyun Han (Faculte Saint-Jean), Roseline Godbout, a professor in the Department of Oncology and member of the Cancer Research Institute of Northern Alberta (CRINA), and others in the Godbout lab.