Abstract
Malignant tumors still pose serious threats to human health due to their high morbidity and mortality. Recurrence and metastasis are the most important factors affecting patient prognosis. Chemotherapeutic drugs and radiation used to treat these tumors mainly interfere with tumor metabolism, destroy DNA integrity, and inhibit protein synthesis. The upregulation of small ubiquitin-like modifier (SUMO) is a prevalent posttranslational modification (PTM) in various cancers and plays a critical role in tumor development. The dysregulation of SUMOylation can protect cancer cells from stresses exerted by external or internal stimuli. SUMOylation is a dynamic process finely regulated by SUMOylation enzymes and proteases to maintain a balance between SUMOylation and deSUMOylation. An increasing number of studies have reported that SUMOylation imbalance may contribute to cancer development, including metastasis, angiogenesis, invasion, and proliferation. High level of SUMOylation is required for cancer cells to survive internal or external stresses. Downregulation of SUMOylation may inhibit the development of cancer, making it an important potential clinical therapeutic target. Some studies have already begun to treat tumors by inhibiting the expression of SUMOylation family members, including SUMO E1 or E2. The tumor cells become more aggressive under internal and external stresses. The prevention of tumor development, metastasis, recurrence, and radiochemotherapy resistance by attenuating SUMOylation requires further exploration. This review focused on SUMOylation in tumor cells to discuss its effects on tumor suppressor proteins and oncoproteins as well as classical tumor pathways to identify new insights for cancer clinical therapy.
Highlights
The cells in our body are exposed to various stimuli from external or internal environments
SUMO interaction motif (SIM)-dependent SUMOylation can modify multiple sites including lysine residues that are not contained in the consensus motifs; and (c) since lysine residues in some target proteins cannot be reached by the ubiquitin-conjugating enzyme 9 (Ubc9)-small ubiquitin-like modifier (SUMO) thioester, E3 ligase acts like a bridge to interact with the target protein and the Ubc9-SUMO thioester
PIAS4 could promote the activity of hypoxia signaling pathway by interacting with VHL, which leads to VHL SUMOylation and impairing VHL’s function in pancreatic cancer cells [133]
Summary
The cells in our body are exposed to various stimuli from external or internal environments. The appropriate responses of cells to these stimuli are key for proliferation, apoptosis, and differentiation. When these responses are dysregulated, cellular development is no longer controlled, which may lead to tumor development [1, 2]. SUMOylation mainly occurs in the lysine residues of proteins [5], which may act as competitors or prerequisites for ubiquitination and play an important role in maintaining protein stability and improving the stress capacity of cells [6,7,8,9]. SUMOylation is a key point in the dysfunction of tumor suppressor proteins and oncoproteins as well as some cancer-related pathways that are common in tumors
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