Boija Ann, Klein Isaac A, Young Richard A
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Cancer Cell. 2021 Feb 8;39(2):174-192. doi: 10.1016/j.ccell.2020.12.003. Epub 2021 Jan 7.
Malignant transformation is characterized by dysregulation of diverse cellular processes that have been the subject of detailed genetic, biochemical, and structural studies, but only recently has evidence emerged that many of these processes occur in the context of biomolecular condensates. Condensates are membrane-less bodies, often formed by liquid-liquid phase separation, that compartmentalize protein and RNA molecules with related functions. New insights from condensate studies portend a profound transformation in our understanding of cellular dysregulation in cancer. Here we summarize key features of biomolecular condensates, note where they have been implicated-or will likely be implicated-in oncogenesis, describe evidence that the pharmacodynamics of cancer therapeutics can be greatly influenced by condensates, and discuss some of the questions that must be addressed to further advance our understanding and treatment of cancer.
恶性转化的特征是多种细胞过程失调，这些过程一直是详细的遗传学、生物化学和结构研究的主题，但直到最近才有证据表明，其中许多过程发生在生物分子凝聚物的背景下。凝聚物是无膜结构，通常由液-液相分离形成，将具有相关功能的蛋白质和RNA分子分隔开来。凝聚物研究的新见解预示着我们对癌症细胞失调的理解将发生深刻变革。在这里，我们总结了生物分子凝聚物的关键特征，指出它们在肿瘤发生中已涉及或可能涉及的方面，描述了癌症治疗药物动力学可受凝聚物极大影响的证据，并讨论了为进一步推进我们对癌症的理解和治疗而必须解决的一些问题。
