Metastasis is thought to be the main cause of cancer death. However, it has been slow in the process of preventing and treating migratory cancer cells.  A research team from Harvard Medical School has identified that an overabundance of a cell receptor named Frizzled-2, along with its activator, Wnt5, appears to raise a tumor’s likelihood of metastasizing. It could trigger the process known as the epithelial-mesenchymal transition(EMT). Their study may help researchers better understand how metastasis begins and inform the design of new treatments to combat it. This finding was published in Cell.

EMT generally plays a role in human development, allowing specific cells to become mobile and invasive. Then, they would move around and form new structures in the growing embryo. Previous researches have linked EMT to cancer metastasis, where tumor cells acquire those properties to disastrous effect. Nevertheless, the mechanism of this progress is still unknown.

In this study, scientists focus on the question “what makes one type of tumor metastasize and another type not?” and discovered a brand-new cell signaling pathway on the basic biology level.

After learning the importance of Frizzled-2, they also developed an antibody to block it . The antibody could curb metastasis in mice with certain type of tumors. In addition, frizzled-2 provides a promising new therapeutic target to prevent or delay metastasis, and both Frizzled-2 and Wnt5 are potential biomarkers that can be used to identify which patients are most at risk of metastasis and could benefit from frizzled-2-directed therapy.

They also found that Wnt and its receptor, Frizzled-2, were present at higher than normal levels in metastatic liver, breast, lung and colon cancer cell lines. In tissue samples from 48 cancer patients, Frizzled-2 was higher in late-stage cancers than in early-stage cancers. The team then painstakingly pieced together the players linking Wnt5 with the onset of metastatic behavior and discovered a previously unknown Wnt pathway. Frizzled-2 it turned out , could activate STAT3, which is known to drive cancer through.

The researchers are confident that their discovery can be translated into a novel therapeutic option for patients in the future.

Reference:

Gujral T S, Chan M, Peshkin L, et al. A Noncanonical Frizzled2 Pathway Regulates Epithelial-Mesenchymal Transition and Metastasis[J]. Cell, 2014, 159(4): 844-856.