Nucleolar Follistatin Promotes Cancer Cell Survival under Glucose-deprived Conditions through Inhibiting Cellular rRNA Synthesis
Nucleolar Follistatin Promotes Cancer Cell Survival under Glucose-deprived Conditions through Inhibiting Cellular rRNA Synthesis
复制标题
核仁卵泡抑素通过抑制细胞 rRNA 合成促进缺糖条件下癌细胞的存活
DOI：
10.1074/jbc.m110.144477
复制
发表时间：
2010-11-19
影响因子：
4.8
通讯作者：
Xu, Zhengping
中科院分区：
文献类型：
--
作者：
Gao, Xiangwei;Wei, Saisai;Xu, Zhengping
实体瘤的发展经常伴随着能量不足的情况，如葡萄糖剥夺和缺氧。卵泡抑素（Follistatin， FST）是一种最初从卵巢卵泡液中发现的分泌蛋白，已被认为参与肿瘤的发展。然而，在缺乏能量的条件下，它是否在癌细胞存活中起作用仍然是一个谜。在本研究中，我们证明了葡萄糖剥夺显著增强HeLa细胞中FST的表达和核仁定位。FST的核仁定位依赖于由64 ~ 87残基组成的核定位信号（NLS）。FST定位于核核减弱了rRNA合成，而rRNA合成是细胞能量稳态和细胞存活的关键过程。FST的过表达延迟了葡萄糖剥夺诱导的细胞凋亡，而FST的下调则起到相反的作用。这些功能依赖于完整的NLS的存在，因为NLS缺失的FST突变体失去了rRNA抑制作用和细胞保护作用。总之，我们发现了FST的一种新的核核功能，这在葡萄糖剥夺对癌细胞存活的调节中很重要。
Solid tumor development is frequently accompanied by energy-deficient conditions such as glucose deprivation and hypoxia. Follistatin (FST), a secretory protein originally identified from ovarian follicular fluid, has been suggested to be involved in tumor development. However, whether it plays a role in cancer cell survival under energy-deprived conditions remains elusive. In this study, we demonstrated that glucose deprivation markedly enhanced the expression and nucleolar localization of FST in HeLa cells. The nucleolar localization of FST relied on its nuclear localization signal (NLS) comprising the residues 64-87. Localization of FST to the nucleolus attenuated rRNA synthesis, a key process for cellular energy homeostasis and cell survival. Overexpression of FST delayed glucose deprivation-induced apoptosis, whereas down-regulation of FST exerted the opposite effect. These functions depended on the presence of an intact NLS because the NLS-deleted mutant of FST lost the rRNA inhibition effect and the cell protective effect. Altogether, we identified a novel nucleolar function of FST, which is of importance in the modulation of cancer cell survival in response to glucose deprivation.