Mysteries of Metastasis Revealed
Metastasis is the process by which cancer cells spread from the site of the original tumour to one or many other places in the body. More than 90% of all cancer suffering and death are associated with metastasis. It is the single most significant challenge to deal with the disease.
A research group from Systems Biology at Harvard Medical School have recently discovered the molecular mechanism of metastasis.
The team demonstrated that an overabundance of a cell receptor called Frizzled-2, and its activator, Wnt5, appears to raise a tumour’s chance to metastasize by triggering a process known as the epithelial-mesenchymal transition (EMT).
EMT is a process by which certain cells become mobile and invasive so they can move throughout the body and form new structures in the growing embryo, thus playing an important role in human development. Some earlier studies have shown the connection of EMT with cancer metastasis, but the exact mechanism has not been explained.
It was also known that, cell signalling pathways activated by the Wnt (“wint”) protein family, influence EMT, but the actual process was not known. So the researchers examined various Wnt signals, and their target Frizzled family of receptors in various cancer cell lines. They found that Wnt5 and its receptor, Frizzled-2, were present at higher levels in metastatic liver, breast, lung and colon cancer cell lines. Moreover Frizzled-2 was observed to be higher in late-stage cancer tissues than in early-stage ones. And an association with high levels of Frizzled-2 with low mortality was also noticed in patients with late-stage liver cancer. Furthermore they demonstrated a novel pathway connecting Wnt5 with the onset of metastasis. Frizzled-2, it turned out, could activate STAT3, which is known to drive cancer through EMT.
Moreover the researchers developed an antibody against Frizzled-2 to block it. They found that the antibody limited metastasis in mice with certain types of tumours. They are now pursuing further studies with the hope that this anti-Frizzled-2 could be useful as a metastasis-fighting drug.
The experts think that Frizzled-2 should be explored as a promising therapeutic target to prevent or delay metastasis. Both Frizzled-2 and Wnt5 could also be considered as the potential biomarkers for detection of metastasis prone patients and patient survival. The other members of the pathway should also be identified to have a full understanding of EMT in cancer and beyond.
A Noncanonical Frizzled2 Pathway Regulates Epithelial-Mesenchymal Transition and Metastasis.Taranjit S. Gujral, Marina Chan, Leonid Peshkin, Peter K. Sorger, Marc W. Kirschner, Gavin MacBeath. DOI: http://dx.doi.org/10.1016/j.cell.2014.10.032
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