Lulling the Cancer Cell into an Eternal Sleep.

A hallmark of metastasis is the ability of cancer cells to undergo the epithelial-to-mesenchymal transition to invade and disseminate to distal sites. More recently, the case has been made that the critical last step in metastasis is dependent on the ability to undergo reversion to an epithelial phenotype in a process known as the mesenchymal-to-epithelial transition (MET). It is this transition in the metastatic cascade that researchers are focusing on clinically to treat disseminated disease. Shinde and colleagues identified spleen tyrosine kinase (SYK) as a critical mediator of MET that facilitated the removal of P-bodies during autophagy. Remarkably, pharmacologic inhibition of SYK inhibited the clearance of P-bodies and autophagy in preclinical models of metastasis, arresting cancer cells in an indefinite dormant state and preventing tumor cell colonization and thus the establishment of aggressive metastatic disease.See related article by Shinde et al., p. 1831. ©2019 American Association for Cancer Research.