A mutant chaperone is a good chaperone

A new genetic variant in a chaperone protein that quells tumor progression and improves responses to therapy is reported in a study published online this week in Nature Medicine. While chaperone inhibitor compounds are being explored for cancer therapy, these findings present a naturally occurring inhibitor.

Microsatellite instability (MSI), a genetic condition that leads to the accumulation of genetic alterations, also characterizes a subset of colon cancers with better prognosis.

Alex Duval and colleagues found that a new genetic variant arising from genomically unstable MSI generates a truncated chaperone — proteins that are key to maintaining the structural stability of other proteins. As normal chaperones inadvertently aid tumor growth by providing cancer cells with shipshape building blocks, MSI tumors with the crippled chaperone are less aggressive in growth and respond better to therapies.