Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Trends Cell Biol. 2024 Jul;34(7):566-577. doi: 10.1016/j.tcb.2024.04.009. Epub 2024 May 27.
Biomolecular condensates, the membraneless cellular compartments formed by liquid-liquid phase separation (LLPS), represent an important mechanism for physiological and tumorigenic processes. Recent studies have advanced our understanding of how these condensates formed in the cytoplasm or nucleus regulate Hippo signaling, a central player in organogenesis and tumorigenesis. Here, we review recent findings on the dynamic formation and function of biomolecular condensates in regulating the Hippo-yes-associated protein (YAP)/transcription coactivator with PDZ-binding motif (TAZ) signaling pathway under physiological and pathological processes. We further discuss how the nuclear condensates of YAP- or TAZ-fusion oncoproteins compartmentalize crucial transcriptional co-activators and alter chromatin architecture to promote oncogenic programs. Finally, we highlight key questions regarding how these findings may pave the way for novel therapeutics to target cancer.
生物分子凝聚物是由液-液相分离(LLPS)形成的无膜细胞区室,代表了生理和肿瘤发生过程中的一个重要机制。最近的研究增进了我们对这些在细胞质或核内形成的凝聚物如何调节 Hippo 信号的理解,Hippo 信号是器官发生和肿瘤发生的核心参与者。在这里,我们综述了最近关于生物分子凝聚物在调节 Hippo-yes 相关蛋白(YAP)/含有 PDZ 结合基序的转录共激活因子(TAZ)信号通路的动态形成和功能的发现,该信号通路在生理和病理过程中。我们进一步讨论了 YAP 或 TAZ 融合癌蛋白的核凝聚物如何分隔关键转录共激活因子,并改变染色质结构以促进致癌程序。最后,我们强调了关于这些发现如何为针对癌症的新型治疗方法铺平道路的关键问题。