Protein Stability Regulation in Osteosarcoma: The Ubiquitin-like Modifications and Glycosylation as Mediators of Tumor Growth and as Targets for Therapy

Abstract

The identification of new therapeutic targets and the development of innovative therapeutic approaches are the most important challenges for osteosarcoma treatment. In fact, despite being relatively rare, recurrence and metastatic potential, particularly to the lungs, make osteosarcoma a deadly form of cancer. In fact, although current treatments, including surgery and chemotherapy, have improved survival rates, the disease’s recurrence and metastasis are still unresolved complications. Insights for analyzing the still unclear molecular mechanisms of osteosarcoma development, and for finding new therapeutic targets, may arise from the study of post-translational protein modifications. Indeed, they can influence and alter protein structure, stability and function, and cellular interactions. Among all the post-translational modifications, ubiquitin-like modifications (ubiquitination, deubiquitination, SUMOylation, and NEDDylation), as well as glycosylation, are the most important for regulating protein stability, which is frequently altered in cancers including osteosarcoma. This review summarizes the relevance of ubiquitin-like modifications and glycosylation in osteosarcoma progression, providing an overview of protein stability regulation, as well as highlighting the molecular mediators of these processes in the context of osteosarcoma and their possible targeting for much-needed novel therapy.

The prognostic value of ubiquitin/ubiquitin-like-related genes along with immune cell infiltration and clinicopathological features in osteosarcoma

“…To date, progress in improving long-term survival in elderly patients with metastatic osteosarcoma has been disappointing. Accumulating evidence shows that Ub/UBL-related genes play important roles in the survival of patients with osteosarcoma [ 19 – 22 ].…”

“…Moreover, dysregulation of these functions is closely related to cancer [ 9 , 12 – 18 ]. More importantly, several Ub/UBL-related genes have recently been shown to have prognostic value in osteosarcoma [ 19 – 22 ]. The ubiquitin-like protein FAT10 has been identified as a promoter of osteosarcoma growth [ 20 , 23 ].…”