Folate is a B9 vitamin which acts as single-carbon donor, and is essential for nucleotide and methionine synthesis. The Reduced Folate Carrier is present on the surface of all cells and mediates the uptake of folate . In contrast, the GPI-anchored Folate Receptor, which binds folate and the synthetic B9 vitamin folic acid with high affinity, is highly expressed on the surface of many types of cancer cells. However, the role of the Folate Receptor in tumourigenesis remains elusive [2, 3]. In general, lack of dietary folate is associated with an increased cancer risk, however; an emerging body of evidence suggest that folic acid supplemented food may enhance the development and progression of already existing pre-malignant and malignant lesions [4, 5].
We have shown that addition of folic acid to HeLa cells can activate the oncogene signal transducer and activator of transcription 3 (STAT3) via a novel Folate Receptor dependent signal transduction pathway, thereby leading to increased cell proliferation. In addition, the common IL-6 signalling receptor gp130 has been identified as a putative co-receptor using siRNA knockdown experiments. Furthermore, we have shown that tumour growth is enhanced in a breast cancer mouse model (PyMT mice), when the mice are on a folic acid enriched diet. Currently, we are investigating if folic acid can activate STAT3 via a murine Folate Receptor in primary cells from PyMT breast tumours.
In conclusion, the activation of the STAT3 oncogene by folic acid may offer a new explanation for the finding by us and others, that a folic acid rich diet can promote the growth of already existing tumours.