靶向相分离:肝细胞癌一种有前景的治疗选择。
Targeting phase separation: a promising treatment option for hepatocellular carcinoma.
作者信息
Zhou Ziling, Jin Sikan, Li Xiaoming, Zhang Dan, Zhang Shengxi, Zhou He, Cai Ji, Song Tao, Wang Xianyao, Kong Qinghong, Tang Zhengzhen, Tan Jun, Zhang Jidong
机构信息
Department of Immunology, Zunyi Medical University, Zunyi, 563000, China.
Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China.
出版信息
Cell Commun Signal. 2025 Sep 1;23(1):387. doi: 10.1186/s12964-025-02406-6.
The spontaneous phenomena known as liquid-liquid phase separation (LLPS) is caused by weak interactions between substances. Under specific circumstances, macromolecules like proteins and nucleic acids can dynamically aggregate to form biomolecular condensates. This phenomenon offers a novel perspective on the intricate spatiotemporal coordination within living cells. Recent research has shown that LLPS is crucial for the initiation and progression of cancer, mainly by influencing multiple cellular activities such as metabolism, autophagy, stress responses, immune reactions, transcriptional regulation and intracellular signaling pathways, etc. Dysregulation of LLPS significantly affects the proliferation, metastasis, and therapeutic resistance of hepatocellular carcinoma (HCC) cells. Here, we introduce recent advances in understanding how LLPS regulates HCC-associated signaling pathways. Furthermore, we discuss the molecular mechanisms underlying the LLPS of oncogenic signaling molecules and its potential implication. Finally, we summarize several feasible approaches for treating HCC by targeting LLPS. These findings have the potential to establish a novel theoretical framework and therapeutic hypothesis for cancer treatment, thus providing more precise and individualized clinical strategies and significantly enhance patient prognosis and overall survival rates.
被称为液-液相分离(LLPS)的自发现象是由物质间的弱相互作用引起的。在特定情况下,蛋白质和核酸等大分子可动态聚集形成生物分子凝聚物。这一现象为活细胞内复杂的时空协调提供了新视角。近期研究表明,LLPS对癌症的发生和发展至关重要,主要通过影响多种细胞活动,如代谢、自噬、应激反应、免疫反应、转录调控和细胞内信号通路等。LLPS失调显著影响肝细胞癌(HCC)细胞的增殖、转移和治疗抗性。在此,我们介绍了在理解LLPS如何调节HCC相关信号通路方面的最新进展。此外,我们讨论了致癌信号分子LLPS的分子机制及其潜在意义。最后,我们总结了几种通过靶向LLPS治疗HCC的可行方法。这些发现有可能为癌症治疗建立新的理论框架和治疗假说,从而提供更精确和个性化的临床策略,并显著提高患者预后和总生存率。