Polo-like kinase 1 (PLK1) is a key cell cycle regulator implicated in the development of various cancers, including prostate cancer. However, the functions of PLK1 beyond cell cycle regulation remain poorly characterized. Here, we report that PLK1 overexpression in prostate epithelial cells triggers oncogenic transformation. It also results in dramatic transcriptional reprogramming of the cells, leading to epithelial-to-mesenchymal transition (EMT) and stimulation of cell migration and invasion. Consistently, PLK1 downregulation in metastatic prostate cancer cells enhances epithelial characteristics and inhibits cell motility. The signaling mechanisms underlying the observed cellular effects of PLK1 involve direct PLK1-dependent phosphorylation of CRAF with subsequent stimulation of the MEK1/2-ERK1/2-Fra1-ZEB1/2 signaling pathway. Our findings highlight novel non-canonical functions of PLK1 as a key regulator of EMT and cell motility in normal prostate epithelium and prostate cancer. This study also uncovers a previously unanticipated role of PLK1 as a potent activator of MAPK signaling.Living cells grow and divide via a series of events called the cell cycle. If this process is disturbed in animals, it can lead to cancer. In the later stages of tumor development, cancer cells frequently change their structure and behavior in a process called the epithelial-to-mesenchymal transition (EMT), which enables them to migrate and form new tumors around the body.A protein called Polo-like kinase 1 (PLK1) plays a central role in the cell cycle and has been implicated in the development of various cancers, including prostate cancer. Recent evidence suggests that PLK1 also has other roles in cells, but it is not clear how much they contribute to the development of cancer.Wu et al. studied PLK1 in human cells and mice and showed that manipulating healthy prostate epithelial cells to produce more PLK1 caused the cells to go through the EMT and increased their ability to migrate. In other experiments, the levels of PLK1 in prostate cancer cells were deliberately lowered, which caused the cells to change to become more like epithelial cells and become less mobile. Wu et al. also investigated how PLK1 promotes the EMT and cell migration. These experiments showed that PLK1 activates a protein that controls an important chain of signaling events called the ERK/MAPK pathway, which is essential for cell growth and migration.Wu et al.’s findings uncover a new role for PLK1 in promoting the spread of cancer cells around the body. A future challenge is to find out how PLK1 is regulated in people with prostate cancer and whether the EMT is involved in promoting other processes in cancer cells.
Wu, J., Ivanov, A. I., Fisher, P. B., & Fu, Z. (2016). Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling. ELife, 5. https://doi.org/10.7554/elife.10734