Abstract
Ubiquitination, a multifaceted post-translational modification, regulates protein function, degradation, and gene expression. The pivotal role of ubiquitination in the pathogenesis and progression of cancer, including colorectal, breast, and liver cancer, is well-established. Osteosarcoma, an aggressive bone tumor predominantly affecting adolescents, also exhibits dysregulation of the ubiquitination system, encompassing both ubiquitination and deubiquitination processes. This dysregulation is now recognized as a key driver of osteosarcoma development, progression, and chemoresistance. This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways. We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function. Finally, we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy. By unraveling the impact of ubiquitination on osteosarcoma cell physiology, we aim to facilitate the development of novel strategies for prognosis, staging, treatment, and overcoming chemoresistance.