title: Nucleolar follistatin promotes cancer cell survival under glucose-deprived conditions through inhibiting cellular rRNA synthesis.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Gao
authors.forename: Saisai
authors.initials: S
authors.lastname: Wei
authors.forename: Kairan
authors.initials: K
authors.lastname: Lai
authors.forename: Jinghao
authors.initials: J
authors.lastname: Sheng
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Su
authors.forename: Junqiao
authors.initials: J
authors.lastname: Zhu
authors.forename: Haojie
authors.initials: H
authors.lastname: Dong
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002466:Cell Nucleolus / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D005260:Female; D005455:Fluorescent Antibody Technique; D038681:Follistatin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency*; D006367:HeLa Cells; D006801:Humans; D019913:Nuclear Localization Signals; D012333:RNA, Messenger / Q000235:genetics; D012335:RNA, Ribosomal / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C503233:FST protein, human; D038681:Follistatin; D019913:Nuclear Localization Signals; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D005947:Glucose