Cold Spring Harbor Laboratory researchers have identified a protein, called FER, that appears to be involved in the metastatic process of ovarian cancer cells though the activation of an important signaling pathway in these cells. The finding may lead to new therapies that can impair the spread of ovarian cancer cells.
Ovarian cancer is known as a “silent killer” because it is often detected at an advanced stage, when the tumor cells have already spread to other parts of the body. About two thirds of women with the disease are diagnosed at Stage 3 or later, when metastasis is already present.
“The statistics point to the urgent need to address advanced disease — metastasis — in ovarian cancer,” Gaofeng Fan, PhD, a postdoctoral investigator who conducted most of the experiments in the laboratory of his mentor,Professor Nicholas K. Tonks, said in a press release. “The problem is especially difficult because of a feature specific to this form of cancer: ovarian cells move around readily within the peritoneal cavity, via the peritoneal fluid, both under normal conditions, and also, unfortunately, when cancer is present.
“Thus, in addition to being able to colonize other sites in the body via blood vessels, ovarian cancer cells have another way of migrating. It’s very hard to render patients free of the disease via surgery due to this diffusion feature.”
Fan and his team found that ovarian cancer cells have high levels of FER, a protein that can add phosphate to other proteins. One such protein that is phosphorylated and activated by FER is MET. MET is overexpressed in up to 60 percent of tumors from patients with ovarian cancer, and has been shown to play a crucial role by inducing cancer cells’ motility and invasiveness. Although MET is commonly activated by its ligand hepatocyte growth factor (HGF), the researchers found that FER is able to activate MET in an HGF-independent manner.
Previous studies have shown that MET inhibitors have little anti-tumor effects when administered alone. “It seems ovarian cancer cells are finding other ways to activate pro-cancer signaling ‘downstream’ of MET,” said Fan. Now, researchers demonstrated that ovarian cancer cells that lack FER have an impaired ability to metastasize. This study suggests that combining MET and FER inhibitors may more effectively limit MET activation and prevent cells from spreading.
“We showed FER was essential for ovarian cancer cell motility and invasiveness, both in vitro and in vivo,” said Tonks. “Considering that frequent amplification of MET accounts for resistance to therapies now in development and to poor prognosis, not only in ovarian cancer but in other cancers too, our findings pinpoint an important new signaling hub, involving the role of FER in MET activation. This may provide a novel strategy for therapeutic intervention, perhaps a drug to suppress FER being administered along with a MET inhibitor.”