The role of cellular plasticity as the crucial motor for the metastasis of differentiated carcinomas.

Abstract

Metastasis is of great clinical importance as it is responsible for more than 90% of cancer-related mortality. Therefore, there is a strong need to prevent metastasis formation or to target existing metastases. It is currently assumed that initiating the epithelial-mesenchymal transition (EMT) process in differentiated cancers may strongly increase the migration potential and invasiveness of cancer cells. Molecular changes occurring during EMT are accompanied by morphological changes, the effect of which is the change of the epithelial phenotype to the mesenchymal one and the acquisition by cancer cells of increased mobility and the ability to invade. After metastasis is formed at a site distant from the primary tumor, cancer cells undergo the reverse process, the mesenchymal-epithelial transition (MET), regaining the epithelial phenotype. This ability of the tumour cell to switch from one state to the other  allows permanent adaptations to the demanding conditions of a changing environment and promotes the formation of metastasis.

In this review, I discuss two principle types of metastatic progression: phenotypic plasticity involving transient EMTâMET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state.

This simplified classification integrates clinically relevant aspects of dormancy, metastatic tropism and therapy resistance, and implies perspectives on treatment strategies against metastasis