E2F1, more than just a cell-cycle controller. Metabolic reprogramming, EMT, metastasization and opportunities for treatment mediated by E2F1 and its coregulators in Cancer.

E2F1 has been defined as an important regulator of the cell cycle many years ago, but since then the number of processes it influences has increased considerably, to include the epithelial-to-mesenchymal-transition (EMT), angiogenesis, metastatization, metabolism, autophagy, and, through the loss of its pro-apoptotic ability, the induction of resistance to cellular damage and chemotherapy. Many of these effects are due to the dysregulation of the CDK-RB-E2F pathway, including changes in the composition of its binding partners, leading to the acquisition of malign properties. E2F1 and its co-factors contribute to several cancer hallmarks. Some, such as unregulated proliferation, resistance to apoptosis and tolerance to genomic instability, have already been studied extensively. In this work I will focus on the non-canonical roles of E2F1, such as the regulation of migration or metabolism, where the interactions between E2F1 and other factors and pathways is key, and on the opportunities for treatment available by targeting E2F1 and its coregulators. First, I will present Almacellas et al. work, showing how E2F1 can activate mTORC1, supporting tumor growth and invasion. Then, through the work of Khan et al. we will overview the various mechanism through which E2F1 promotes metastases. Finally, while no direct inhibitors of E2F1 are available as of yet, a number of strategies have been proposed to interfere with its action. In particular, Goody et al. repurposed a drug to prevent the formation of the E2F1-MTA1 complex, preventing the expression of pro-metastatic genes and the development of metastasis in vivo.