Tumors that produce more stress granules are more likely to metastasize, Somasekharan et al. reveal.
When cells are under duress, they curtail almost all protein synthesis and stash their mRNAs in stress granules. The structures help healthy cells, but they also allow tumor cells to survive harsh conditions. The protein YB-1, which is overexpressed in many types of cancer cells, accumulates in stress granules, but researchers don’t know how YB-1 affects these particles.
Somasekharan et al. found that stressed-out sarcoma cells need YB-1 to assemble stress granules. Knocking down YB-1 decreased levels of one stress granule protein, G3BP1. The team determined that YB-1 attaches to the mRNA for G3BP1 and stimulates its translation.
To determine the effects of YB-1 in vivo, the researchers implanted mice with sarcomas that either made or lacked the protein. A month later, cells in the control tumors carried more stress granules than did the tumor cells missing YB-1. Somasekharan et al. then implanted mice with tumors that either produced or lacked G3BP1. The control tumors harbored more stress granules than did the G3BP1-deficient tumors, and only the control tumors metastasized.
The researchers aren’t sure how the reduction in stress granules curbs metastatic spread. The structures might lock away mRNAs for proteins that prevent cells from moving. The results suggest that drugs to inhibit stress granule formation might rein in cancer metastasis.
Text by Mitch Leslie