Signaling Pathway Found to Cause Apoptosis in Cancer Cells

Activins are proteins involved in a number of important biological functions, including the regulation of the menstrual cycle, metabolism, homeostasis, immune response, wound repair, and endocrine function. In a study published today in Developmental Cell, researchers show that when activin B and its receptor, ALK7, are expressed by cancer cells, they can form a ‘barrier’ that prevents them not only from forming new tumors but also from metastasizing.

The researchers studied the ALK7 signaling pathway in mice with either pancreatic neuroendocrine tumors or breast cancer. They found that when the receptor is activated by activin B, cancer cells died via a process called apoptosis. On the contrary, blocking ALK7 activation allowed cancer cells to evade death and successfully metastasize to various organs, such as the liver, lungs, and brain. And the way by which cancer cells evaded the activin B/ALK7 ‘barrier’ was by downregulating either activin B or ALK7.

“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 senior author Douglas Hanahan.

Furthermore, this study also revealed that the presence of ALK7 correlated with prolonged relapse-free survival of patients with various cancers, including breast cancer. Notably, comparatively higher levels of ALK7 expression were also associated with a longer period before metastasis became apparent in breast-cancer patients.

“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 first author Iacovos Michael.