title: SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing β-catenin biosynthesis.
abstract: Wnt/β-catenin signalling is widely implicated in embryogenesis, tissue homeostasis and tumorigenesis. The key event in Wnt signalling activation is β-catenin accumulation, which is controlled by both its production and degradation. However, much more emphasis has been placed on the understanding of its degradation. Here, we show that the synthesis of β-catenin protein, which requires a group of serine/arginine-rich splicing factors (SRSF), also contributes to its tumorigenic activity. Overexpression of SRSF1 and SRSF9 promote β-catenin accumulation via the recruitment of β-catenin mRNA and by enhancing its translation in an mTOR-dependent manner. We further demonstrate that, like SRSF1, SRSF9 is also an oncogene, and is frequently overexpressed in multiple types of human tumours. Finally, our results suggest that promoting degradation and blocking production of β-catenin synergistically reduce β-catenin levels under pathological conditions and that a combinational therapy could be a promising approach for the treatment of cancer patients.
authors.affiliation: Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.forename: Binlu
authors.initials: B
authors.lastname: Huang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shi
authors.forename: Jiayu
authors.initials: J
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Huangfu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000068103:Serine-Arginine Splicing Factors; D058570:TOR Serine-Threonine Kinases