SUMO and the robustness of cancer

Key Points Reversible post-translational protein modification by small ubiquitin-like modifier (SUMO), sumoylation, is a crucial mechanism in the maintenance of genomic integrity, in the regulation of proper gene expression patterns and in numerous signal transduction pathways and is thus essential for cell and tissue homeostasis in all eukaryotes. Numerous protein complexes contain multiple sumoylated proteins, suggesting that sumoylation regulates not only the activity of individual substrates but that of entire functional complexes. Furthermore, in complex signalling pathways, sumoylation frequently targets multiple elements, in some cases antagonizing the activity of one element while promoting that of another within the same pathway. Various biotic and abiotic stresses substantially alter the level of global cellular sumoylation. Importantly, numerous human tumours display marked upregulation of SUMO pathway components. This 'SUMOness' of cancers may indeed be required by tumour cells to maintain the robustness of compromised or otherwise easily misregulated gene expression programmes and signalling pathways. Sumoylation would therefore contribute substantially to cancer cell survival and proliferation in a potentially hostile microenvironment. Although strong inhibition of global cellular sumoylation carries obvious risks for all cells, partial or temporary inhibition may be sufficient to expose certain tumour-specific vulnerabilities (for example, susceptibility to inducers of apoptosis and/or senescence) and therefore could provide a promising approach for future therapeutic intervention in some settings. Sumoylation is an important mechanism in cellular responses to stress, and appears to be upregulated in many cancers. This Review argues that sumoylation protects the stability and functionality of otherwise easily misregulated gene expression programmes and signalling pathways of cancer cells. Post-translational protein modification by small ubiquitin-like modifier (SUMO), termed sumoylation, is an important mechanism in cellular responses to stress and one that appears to be upregulated in many cancers. Here, we examine the role of sumoylation in tumorigenesis as a possibly necessary safeguard that protects the stability and functionality of otherwise easily misregulated gene expression programmes and signalling pathways of cancer cells.