Kearns Bridger, McKell Andralyn, Steveson Isaac, Worley Peyton, Barton Braeden, Bennett Jordan, Anderson DeLaney, Harris Jacob, Christensen James, Barrott Jared J
Department of Cell Biology & Physiology, Brigham Young University, Provo, UT 84602, USA.
Simmons Center for Cancer Research, Brigham Young University, Provo, UT 84602, USA.
Int J Mol Sci. 2025 May 13;26(10):4644. doi: 10.3390/ijms26104644.
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, has emerged as a pivotal tumor suppressor altered in a broad range of human malignancies. Its frequent inactivation across diverse cancer types has revealed pleiotropic roles that intersect multiple Hallmarks of Cancer. In this review, we integrate current knowledge on how ARID1A loss influences cellular processes including proliferative signaling, resistance to cell death, genomic instability, metabolic reprogramming, immune evasion, and more. We discuss the context-specific consequences of ARID1A deficiency, its cooperation with other oncogenic events, and its implications for therapeutic vulnerability-particularly in the realm of synthetic lethality and immune modulation. By mapping ARID1A's functional impact onto the established hallmarks framework, we highlight its centrality in cancer biology and underscore opportunities for biomarker-driven strategies and targeted interventions. Understanding ARID1A's multifaceted roles offers a compelling lens through which to explore chromatin dysregulation in cancer and guide translational advances.
ARID1A是SWI/SNF染色质重塑复合物的一个亚基，已成为在多种人类恶性肿瘤中发生改变的关键肿瘤抑制因子。它在不同癌症类型中频繁失活，揭示了其与癌症多个特征相交的多效性作用。在本综述中，我们整合了当前关于ARID1A缺失如何影响细胞过程的知识，这些过程包括增殖信号传导、对细胞死亡的抗性、基因组不稳定、代谢重编程、免疫逃逸等。我们讨论了ARID1A缺陷在特定背景下的后果、它与其他致癌事件的协同作用及其对治疗易损性的影响，特别是在合成致死和免疫调节领域。通过将ARID1A的功能影响映射到已确立的特征框架上，我们突出了其在癌症生物学中的核心地位，并强调了生物标志物驱动策略和靶向干预的机会。了解ARID1A的多方面作用为探索癌症中的染色质失调和指导转化进展提供了一个引人注目的视角。
