Role of HDAC6 in carcinomas

Histone deacetylase 6 (HDAC6) is the sole member of the histone deacetylase (HDAC) family predominantly localized in the cytoplasm, characterized by dual catalytic domains and an ubiquitin-binding domain. In recent years, it has garnered substantial attention due to its critical role in tumor initiation and progression. This review delineates the unique structural features and core biological functions of HDAC6, while further exploring its expression patterns and prognostic significance in tumors. Additionally, it elaborates on the regulatory roles of HDAC6 in key biological behaviors of tumor cells, including promoting proliferation, suppressing apoptosis, enhancing migratory and invasive potentials, and inducing epithelial-mesenchymal transition (EMT). Concomitantly, the review analyzes the impacts of HDAC6 on the tumor immune microenvironment, its modulation of tumor metabolism, and its association with tumor drug resistance. To date, research on HDAC6 in tumors has firmly established its value as a potential therapeutic target, with specific inhibitors (e.g., ACY-1215 and Tubastatin A) demonstrating significant antitumor activity in preclinical studies and several clinical trials. Focused on the implications of HDAC6 in tumors, this review not only highlights its distinct functions compared to other HDAC family members but also integrates previously unreported mechanisms of action (e.g., HDAC6 cooperates with NEDD8/p62 to sustain proteostasis) and clinical translation perspectives. Collectively, it presents an innovative review that provides valuable references for subsequent basic research and clinical practice of HDAC6-targeted tumor therapy.