e-signal Lab, Department of Biochemistry, Institute of Chemistry, University of São Paulo, Ave Prof. Lineu Prestes 748, São Paulo, SP 05508-000, Brazil.
J Cell Sci. 2022 Aug 1;135(15). doi: 10.1242/jcs.259676. Epub 2022 Aug 5.
Quiescence, the ability to temporarily halt proliferation, is a conserved process that initially allowed survival of unicellular organisms during inhospitable times and later contributed to the rise of multicellular organisms, becoming key for cell differentiation, size control and tissue homeostasis. In this Review, we explore the concept of cancer as a disease that involves abnormal regulation of cellular quiescence at every step, from malignant transformation to metastatic outgrowth. Indeed, disrupted quiescence regulation can be linked to each of the so-called 'hallmarks of cancer'. As we argue here, quiescence induction contributes to immune evasion and resistance against cell death. In contrast, loss of quiescence underlies sustained proliferative signalling, evasion of growth suppressors, pro-tumorigenic inflammation, angiogenesis and genomic instability. Finally, both acquisition and loss of quiescence are involved in replicative immortality, metastasis and deregulated cellular energetics. We believe that a viewpoint that considers quiescence abnormalities that occur during oncogenesis might change the way we ask fundamental questions and the experimental approaches we take, potentially contributing to novel discoveries that might help to alter the course of cancer therapy.
静止，即暂时停止增殖的能力，是一种保守的过程，它最初使单细胞生物能够在不适宜生存的时期存活下来，后来促进了多细胞生物的出现，成为细胞分化、大小控制和组织稳态的关键。在这篇综述中，我们探讨了癌症作为一种疾病的概念，这种疾病涉及到细胞静止在每一个步骤中的异常调节，从恶性转化到转移性生长。事实上，细胞静止调节的破坏与所谓的“癌症的标志”之一相关。正如我们在这里所论证的，静止诱导有助于免疫逃逸和抵抗细胞死亡。相反，静止的丧失则是持续增殖信号、逃避生长抑制因子、促进肿瘤发生的炎症、血管生成和基因组不稳定性的基础。最后，静止的获得和丧失都与复制永生、转移和细胞能量代谢失调有关。我们认为，考虑肿瘤发生过程中出现的静止异常的观点可能会改变我们提出基本问题和采用实验方法的方式，从而有可能为可能有助于改变癌症治疗进程的新发现做出贡献。
