Preclinical experiments at VCU Massey Cancer Center (VA, USA) have led to reports of a novel function of the PLK1 gene, which aids metastasis of prostate cancer cells. Published recently in eLife, the study not only provides new information regarding the role of PLK1 in cancer growth and progression, but also opens up new avenues to explore for novel cancer therapies.
Lead investigator on the study Zheng Fu (VCU Massey Cancer Center) commented, “We challenged a current dogma in the field that emphasized PLK1’s role in mitosis (cell division) as a primary mechanism for cancer growth…We showed that PLK1 drives migration of normal prostate epithelial and prostate cancer cells through an entirely different process.”
The study, conducted using human prostate cancer cell lines, demonstrated that increased expression of PLK1 led to activation of oncogene c-RAF, which has been shown previously to be involved in regulation of cell growth and division. However, c-RAF has also been proven to activate signaling through the MAPK pathway, which is involved in regulating proliferation, gene expression, cell division and apoptosis.
The study showed that enhanced MAPK signaling (due to c-RAF activation) induces the epithelial-to-mesenchymal transition – a biologic process that allows a polarized epithelial cell to undergo various biochemical changes enabling it to assume a mesenchymal cell phenotype, including enhanced migratory capacity, invasiveness and elevated resistance to apoptosis – and thus stimulates the metastasis of prostate cancer cells.
“Our findings could significantly impact the development of PLK1 inhibitors for the treatment of advanced prostate cancer,” stated Fu. “Furthermore, the findings may extend to other cancers because previous research has shown a link between enhanced PLK1 expression and invasiveness of colorectal, breast and thyroid tumors.”
The researchers next plan to carry out further investigations into the link between PLK1 and MAPK signaling in prostate cancer, and also to see whether EMT induced by PLK1 plays a role in any other cancer-promoting processes besides cell migration and metastasis.