SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone

Abstract

Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein and regulate protein function. As fate-determinants of several effectors and mediators, SUMOylation and NEDDylation play relevant roles in many aspects of tumor cell biology. Bone represents a preferential site of metastasis for solid tumors (e.g., breast and prostate cancers) and the primary site of primitive tumors (e.g., osteosarcoma, chondrosarcoma). Deregulation of SUMOylation and NEDDylation affects different aspects of neoplastic transformation and evolution such as epithelial-mesenchymal transition, adaptation to hypoxia, expression and action of tumor suppressors and oncogenic mediators, and drug resistance. Thereby, they represent potential therapeutic targets. This narrative review aims at describing the involvement and regulation of SUMOylation and NEDDylation in tumor biology, with a specific focus on primary and secondary bone tumors, and to summarize and highlight their potentiality in diagnostics and therapeutic strategies.

Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

“…SENPs includes SENP1,SENP2, SENP3,SENP5, SENP6 and SENP7, for every SENP there are specified SUMO proteins [43] . The SUMOylation process is vitally implicated in carcinogenesis, certainly in many cancers the abnormality in SUMOylation enzymes and also in target proteins SUMOylation linked to different cancers [44] .…”

High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential

“…Ubiquitinylation leads to proteasome-mediated degradation of the target protein, while SUMOylation more influences subcellular trafficking or the activity of target protein 27 . GRP75 directly binds to HMGA1 to inhibit the ubiquitinylation and degradation of HMGA1, then upregulates HMGA1 to promote the proliferation and metastasis of lung adenocarcinoma cells by activating JNK/c-JUN signal 28 .…”

CRISPR‐Cas9 screening identified lethal genes enriched in necroptosis pathway and of prognosis significance in osteosarcoma

“…1,2 Originating from mesenchymal-derived primitive transformed cells, this disease has posed significant challenges to the medical community. 3 Despite advances in multi-agent chemotherapy and surgical techniques, the overall survival rates for patients with osteosarcoma have not improved substantially over the past few decades. 4 Hence, there is an urgent need to identify new prognostic markers and novel therapeutic targets for osteosarcoma metastasis cannot be overemphasized.…”

“…Osteosarcoma, a prevalent malignant bone tumor among children and adolescents, represents 2.4% of all malignancies in this age group and possesses a high metastatic potential 1,2 . Originating from mesenchymal‐derived primitive transformed cells, this disease has posed significant challenges to the medical community 3 . Despite advances in multi‐agent chemotherapy and surgical techniques, the overall survival rates for patients with osteosarcoma have not improved substantially over the past few decades 4 .…”