Researchers at the Virginia Commonwealth University School of Medicine found that Polo-like kinase 1 (PLK1) gene overexpression promotes oncogenic transformation and the migration of prostate cancer cells. The findings point the way to potential new therapeutic avenues for prostate and other cancers.
The study, “Polo-like kinase 1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling,” published in eLife,was also presented in a poster session at the 2016 American Association for Cancer Research (AACR) annual meeting.
Mammalian polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in the regulation of the cell cycle, mediating every stage of cell division. The PLK1 gene is overexpressed in several human tumors, and its expression levels are associated with increased cell proliferation and metastatic potential. Importantly, the gene is commonly overexpressed in prostate cancer (>50%), and PLK1 overexpression is linked to higher tumor grade. Recent evidence also suggests that the protein is involved in other cell processes, but any possible link between its role there and cancer development is not yet clear.
Researchers, using human cell lines, investigated the role of PLK1 in the motility of prostate epithelial cells and prostate cancer cells. According to the results, PLK1 promotes the migration of prostate cells by encouraging a process where epithelial cells change into mesenchymal (skeletal) stem cells that can move throughout the body. This process, called epithelial-to-mesenchymal transition (EMT), contributes to cancer spread and poor disease prognosis.
“We challenged a current dogma in the field that emphasized PLK1’s role in mitosis (cell division) as a primary mechanism for cancer growth,” Dr. Zheng Fu, the study’s lead investigator, said in a news release. “We showed that PLK1 drives migration of normal prostate epithelial and prostate cancer cells through an entirely different process.”
Researchers demonstrated that increased PLK1 expression activated an oncogene known as c-RAF, which in turn activated signaling through the mitogen-activated protein kinase (MAPK) pathway. Enhanced MAPK signaling induced EMT, and stimulated prostate cancer cell metastasis.
Downregulation of PLK1 also inhibited the motility of metastatic prostate cancer cells, hinting at a possible new therapeutic strategy. “Our findings could significantly impact the development of PLK1 inhibitors for the treatment of advanced prostate cancer,” Dr Fu said. “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.”
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