Metastasis accounts for a majority of cancer death. One key feature during metastasis is epithelial-mesenchymal transition (EMT), which is regulated by transcription factors such as Snail and Twist. In non-malignant cells, Snail has a short half-life and is degraded via ubiquitination, but its stability is increased in cancer cell. However, the mechanism by which Snail escapes ubiquitination and degradation remains unknown. Recently, we found that Dub3 is a deubiquinase of Snail. Most importantly, we determined that Dub3 responded to extracellular signals such as IL-6, and that the resultant signaling prevented Snail degradation, and promoted cancer growth, invasion, and migration. In this highlight, we present a concise picture of how the transcription factor Snail is regulated by ubiquitination in cancer cells, the role of Dub3 in this process, and its potential use as a treatment target.
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Our research was also supported by grants from NIH (CA125454 and CA188118), DoD (BC140733P1), Mary Kay Ash Foundation (to B.P. Zhou), and American Cancer Society Research Scholar Award (RSG13187) and NIH (P20GM121327) (to Y Wu).
Yu, Qian; Zhou, Binhua P.; and Wu, Yadi, "The Regulation of Snail: On the Ubiquitin Edge" (2017). Pharmacology and Nutritional Sciences Faculty Publications. 62.