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Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1

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机构: [1]Shanghai Jiao Tong Univ, Hongqiao Int Inst Med, Tongren Hosp, Fac Basic Med,Sch Med, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai, Peoples R China [3]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Digest Endoscopy Ctr, Shanghai, Peoples R China [4]Fudan Univ, Huashan Hosp, Dept Gastroenterol, Shanghai, Peoples R China [5]Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China
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关键词: argininosuccinate synthase 1 epithelial-mesenchymal transition metastasis Snail ubiquitination

摘要:
Snail is a dedicated transcriptional repressor and acts as a master inducer of EMT and metastasis, yet the underlying signaling cascades triggered by Snail still remain elusive. Here, we report that Snail promotes colorectal cancer (CRC) migration by preventing non-coding RNA LOC113230-mediated degradation of argininosuccinate synthase 1 (ASS1). LOC113230 is a novel Snail target gene, and Snail binds to the functional E-boxes within its proximal promoter to repress its expression in response to TGF-beta induction. Ectopic expression of LOC113230 potently suppresses CRC cell growth, migration, and lung metastasis in xenograft experiments. Mechanistically, LOC113230 acts as a scaffold to facilitate recruiting LRPPRC and the TRAF2 E3 ubiquitin ligase to ASS1, resulting in enhanced ubiquitination and degradation of ASS1 and decreased arginine synthesis. Moreover, elevated ASS1 expression is essential for CRC growth and migration. Collectively, these findings suggest that TGF-beta and Snail promote arginine synthesis via inhibiting LOC113230-mediated LRPPRC/TRAF2/ASS1 complex assembly and this complex can serve as potential target for the development of new therapeutic approaches to treat CRC.

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出版当年[2020]版:
大类 | 1 区 生物
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
最新[2025]版:
大类 | 1 区 生物学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
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出版当年[2019]版:
Q1 CELL BIOLOGY Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Hongqiao Int Inst Med, Tongren Hosp, Fac Basic Med,Sch Med, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai, Peoples R China
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通讯机构: [1]Shanghai Jiao Tong Univ, Hongqiao Int Inst Med, Tongren Hosp, Fac Basic Med,Sch Med, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai, Peoples R China [3]Shanghai Jiao Tong Univ, Sch Med, Shanghai Tongren Hosp, Digest Endoscopy Ctr, Shanghai, Peoples R China [5]Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China
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