Stress Granules in Cancer.
Stress Granules in Cancer.
复制标题
DOI：
10.1007/112_2020_37
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Grabocka E
中科院分区：
文献类型：
--
作者：
Song MS;Grabocka E
细胞在胞内空间组织复杂生化反应的能力是生命的基本组织原则。这种组织的关键是将细胞质分隔成不同的细胞器，这通常通过细胞内膜实现。然而，最近的证据为细胞区室化增加了一层新的灵活性。因此，响应于特定的刺激，液-液相分离可以导致细胞质快速重排以形成无膜细胞器。应激颗粒（Stress granules，SG）是一种细胞器，当细胞面临应激刺激时，它会特异性地形成，以帮助细胞应对应激。固有地，改变的SG形成已经与包括癌症在内的与应激和炎性病症相关的疾病的发病机制相关联。令人兴奋的发现已经表明SGs和肿瘤发生之间的密切联系。已显示包括RAS癌基因、mTOR和组蛋白脱乙酰酶6（HDAC 6）的几种促肿瘤发生信号分子上调SG形成。基于这些研究，SGs已经成为可以整合致癌信号和肿瘤相关应激刺激以增强癌细胞适应性的结构。此外，在过去的十年中，越来越多的证据表明，SGs不仅可以调节生存和细胞死亡之间的转换，而且还有助于癌细胞增殖，侵袭，转移和耐药性。尽管关于SGs在肿瘤发生中的作用仍有许多有待了解，但这些研究强调SGs是癌症的关键调控中心和有前途的治疗靶点。
The capacity of cells to organize complex biochemical reactions in intracellular space is a fundamental organizational principle of life. Key to this organization is the compartmentalization of the cytoplasm into distinct organelles, which is frequently achieved through intracellular membranes. Recent evidence, however, has added a new layer of flexibility to cellular compartmentalization. As such, in response to specific stimuli, liquid-liquid phase separations can lead to the rapid rearrangements of the cytoplasm to form membraneless organelles. Stress granules (SGs) are one such type of organelle that form specifically when cells are faced with stress stimuli, to aid cells in coping with stress. Inherently, altered SG formation has been linked to the pathogenesis of diseases associated with stress and inflammatory conditions, including cancer. Exciting discoveries have indicated an intimate link between SGs and tumorigenesis. Several pro-tumorigenic signaling molecules including the RAS oncogene, mTOR, and histone deacetylase 6 (HDAC6) have been shown to upregulate SG formation. Based on these studies, SGs have emerged as structures that can integrate oncogenic signaling and tumor-associated stress stimuli to enhance cancer cell fitness. In addition, growing evidence over the past decade suggests that SGs function not only to regulate the switch between survival and cell death, but also contribute to cancer cell proliferation, invasion, metastasis, and drug resistance. Although much remains to be learned about the role of SGs in tumorigenesis, these studies highlight SGs as a key regulatory hub in cancer and a promising therapeutic target.