Snail suppresses cellular senescence and promotes fibroblast-led cancer cell invasion.
Snail, a zinc finger transcription factor, induces an epithelial-mesenchymal transition (EMT) in various cancer and epithelial cells. We investigated the function of Snail (SNAI1) by downregulating its expression with short interfering RNA (siRNA). Suppression of Snail expression induced cellular senescence in several cancer cells and in normal fibroblast IMR90 cells. Cancer progression is facilitated by fibroblasts, so-called fibroblast-led cancer cell invasion. Snail-silenced cancer cells exhibited reduced motility, which was further decreased by cocultivation with Snail-silenced IMR90 cells. Our data suggest that cell motility and cellular senescence, which are regulated by Snail in cancer cells and fibroblasts, modulate fibroblast-led cancer cell invasion. Therefore, we propose that local suppression of Snail in cancer and the cancer microenvironment represents a potent therapeutic strategy.