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Biological barrier could keep cancer from metastasizing

Cancer might not be so difficult to kill if it didn't have the terrifying ability to spread throughout the body. Now, researchers at EPFL, the University of Bern and the Swiss Institute of Bioinformatics have discovered a particular protein signaling pathway that controls whether a tumor can spread or not, making it a good target for future drugs.

The research focused on a cell receptor called ALK7, studying its role in mice with breast cancer or pancreatic neuroendocrine tumors. The team discovered that when activated by the protein activin B, ALK7 triggers a signaling pathway that can kill cancer cells through the process of apoptosis, as well as suppressing metastasis, and preventing new tumors from forming (tumoriogensis).

Never one to give up, cancer often overcomes this barrier by downregulating either activin B, ALK7, or both. Indeed, in their tests the researchers found that blocking ALK7 did allow the cancer cells to survive and spread through the body.

"This study enforces the notion that apoptosis is an important barrier of tumorigenesis, and that its evasion by cancer cells is a key hallmark capability of cancer cells during malignancy and metastasis," says Douglas Hanahan, lead author of the study.

Interestingly, the team also found that higher levels of ALK7 expression in human cancer patients seemed to line up with periods of remission. In other cases, higher levels were found to keep breast cancer metastasis at bay for longer.

"Elucidating how cancer cells manage to overcome nature's various 'safety checkpoints' to prevent malignancy is an important step towards understanding tumor biology and disease pathogenesis," says Iacovos Michael, lead researcher of the team.

Dealing with metastasis is emerging as a key treatment for cancer, and activin B isn't the only protein scientists have in their sights. Other potential targets include proteins that help tumor cells break away and spread, those that protect traveling cancer cells, and those that fuel the whole process. Some studies even go as far to suggest that blocking metastasis is more important than killing cancer itself.

The research was published in the journal Developmental Cell.

May 7, 2019


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