Credit: Courtesy of Thomas Deerinck and Mark Ellisman.

Skeletal muscle wasting, or cachexia, contributes to death in one-third of all cancer patients, but what triggers the muscle wasting is still a mystery. Swarnali Acharyya and colleagues (Cancer Cell 8, 421–432) now show that one of the players in muscular dystrophy, the dystrophin glycoprotein complex (DGC), has a crucial role in cancer cachexia.

This complex forms a bridge between the cytoskeleton and the extracellular matrix to protect muscle cells from injury when they contract. The researchers found that tumor-bearing mice that show muscle wasting also had wrinkled and possibly leaky muscle cell membranes. This phenotype is similar to what has been seen in muscular dystrophy. Normal muscle cells, as shown here, have smooth membranes (laminin, extracellular matrix component, in green; actin in red, DNA in blue).

What's more, key components of the DGC were abnormally modified or their levels reduced in muscle fibers of tumor-bearing mice—affecting the function of the complex. Increasing dystrophin expression in the mouse skeletal muscle could prevent wasting in the tumor model.

The findings may be relevant to humans, as a similar pattern of DGC dysregulation was observed in people with gastrointestinal cancer. Whether the dysregulation occurs as a cause or effect of this wasting is unclear, but it points to a new direction for therapy.