Most cancer deaths occur because of metastasis, yet progress in preventing and treating migratory cancer cells has been slow.

“It’s been particularly challenging to design drugs that work against metastasis,” said Taran Gujral, research fellow in systems biology at Harvard Medical School. “Unfortunately, many cancers aren’t detected until after they’ve already metastasized.”

Like a transformer surge that makes birds on a wire take flight, new research has found that the receptor Frizzled-2 can induce cancer cells to migrate. Image: O'Reilly Science Art

Like a transformer surge that makes birds on a wire take flight, new research has found that the receptor Frizzled-2 can induce cancer cells to migrate. Image: O'Reilly Science Art

 

Gujral and colleagues have now identified a cellular culprit that should help researchers better understand how metastasis begins. Their findings may also inform the design of new treatments to combat it.

As reported Nov. 6 in Cell, the team discovered that an overabundance of a cell receptor called Frizzled-2, along with its activator, Wnt5, appears to raise a tumor’s likelihood of metastasizing by triggering a process known as the epithelial-mesenchymal transition, or EMT.

EMT normally plays a role in human development, allowing certain cells to become mobile and invasive so they can move around and form new structures in the growing embryo. Previous studies have linked EMT to cancer metastasis, where tumor cells acquire those properties to disastrous effect. The question has been: How exactly does that happen?

“This study makes big headway on an extremely important medical problem: what makes one type of tumor metastasize and another type not,” said Marc Kirschner, John Franklin Enders University Professor of Systems Biology at HMS, chair of the Department of Systems Biology and co-senior author of the paper.  

“On a basic biology level, it also reports the unexpected discovery of a brand-new cell signaling pathway,” Kirschner added.

After learning the importance of Frizzled-2, the researchers developed an antibody to block it. The antibody curbed metastasis in mice with certain types of tumors.

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