Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma

We previously identified genes associated with Snail-mediated squamous cell carcinoma (SCC) invasiveness, in which we observed significant elevation of Cyr61 expression. In this study, SCC cell lines overexpressing Cyr61 exhibited constitutive activation of Rho A and upregulated invasiveness without the disruption of homophilic cell attachment. Humoral Cyr61 enhanced further production of endogenous Cyr61 by SCC cells, which stimulated collective cell migration and the development of an invasive tumor nest. We propose a Cyr61-dependent model for the development of invasive SCC nest, whereby a subset of tumor cells that highly produce Cyr61 may direct other tumor cells to undergo collective cell migration, resulting in a formation of primary SCC mass.

► We propose a invasion model of Oral squamous cell carcinomas that consists of EMT-dependent and Cyr61-dependent invasion.
► EMT phenotype cells lead the invasion and prime collective cell migration of other tumor cells with Cyr61 production.
► Humoral Cyr61 invokes the self-production of Cyr61 in the tumor cells, resulting in a formation of tumor nests.