Remodeling of the ARID1A tumor suppressor

• Published in: Cancer letters 2020-10, Vol.491, p.1-10
• Main Authors: Luo, Qingyu, Wu, Xiaowei, Liu, Zhihua
• Format: Article
• Language: English
• Subjects: Ablation; Animals; Apoptosis; Breast cancer; Cancer; Cancer therapies; Carcinogenesis; Cell migration; Cell proliferation; Chromatin Assembly and Disassembly; Chromatin remodeling; Colorectal cancer; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Epigenetic silencing; Gastric cancer; Gene regulation; Histone modification; Humans; miRNA; Mutation; Neoplasms - genetics; Ovarian cancer; Posttranslational modification; Precancerous Conditions - genetics; Protein interaction; Roles; Synthetic lethality; Transcription; Transcription Factors - genetics; Transcription Factors - physiology; Tumor suppressor genes; Tumor Suppressor Proteins - physiology; Tumorigenesis; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2020.07.026

In recent years, AT-rich interactive domain-containing protein 1A (ARID1A) has been widely accepted as a bona fide tumor suppressor due to its essential role in preventing tumorigenesis and tumor progression in both mouse and human contexts. ARID1A shows high mutation frequencies in both cancers and preneoplastic lesions. The loss of ARID1A expression in cancer cells leads to increases in cell proliferation, invasion and migration and reductions in cell apoptosis and chemosensitivity. The tumor-suppressive role of ARID1A is mainly attributed to its regulation of gene transcription, which can be induced either directly by chromatin remodeling or indirectly by affecting histone modifications. ARID1A also acts independently of its cardinal transcription-regulating mechanisms, which include interfering with protein-protein interactions. Interestingly, nonmutational mechanisms, such as regulation by DNA hypermethylation, microRNAs, and ubiquitinases/deubiquitinases, have provided another perspective on ARID1A inactivation in cancer. Since the critical tumor-suppressive role of ARID1A has been revealed, several studies have attempted to identify synthetic lethal targets with ARID1A mutation/inactivation as an alternative strategy for cancer treatment. •ARID1A shows high mutation frequencies in many cancer types.•ARID1A exerts tumor suppressive roles via multiple mechanisms.•Nonmutational events also play an important role in the inactivation of ARID1A in cancer.•Targeting ARID1A gene loss is a promising strategy in cancer treatment.