The Snail protein has a new carcinogenic trick up its sleeve, according to Massoumi et al. on page 221.

In many different types of cancer, the transcriptional repressor Snail helps tumors spread by dampening the expression of the sticky E-cadherin molecules that hold adjacent cells together. Now, Massoumi et al. show that Snail also promotes tumor cell division by shutting off the tumor suppressor CYLD. When Snail was blocked in melanoma cells, the low CYLD expression bounced back, and the cells formed smaller and less aggressive tumors when transferred into mice.

This group had previously found that Snail was abnormally abundant in melanoma cells. They now link increased Snail to a common mutation (V600E) in the kinase BRAF—found in more than half of malignant melanomas in humans—that promotes tumor growth by activating Erk signaling in response to growth factors and cytokines. Indeed, when mutated BRAF was expressed in melanoma cells, Snail levels rose and CYLD levels waned.

CYLD's ability to suppress tumor cell division is due in part to its ability to keep the transcription factor BCL-3 out of the nucleus, where it normally teams up with NF-kB to turn on the cell cycle protein cyclin D1. This pathway was also operational in melanoma cells, the authors found. But in these cells, CYLD also inhibited the expression of N-cadherin, a protein known to promote tumor spread.

By curbing CYLD, Snail thus promotes both tumor growth and spread. Indeed, in skin cancer samples from humans, increased Snail and decreased CYLD correlated with decreased survival.