Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin beta 1
文献类型：期刊论文
| 作者 | Zhao, Gaoxiang2,5; Gong, Liyan2,5; Jin, Yujuan2,5; Guo, Chenchen2,5; Yue, Meiting2,5; Yao, Shun2,5; Qin, Zhen2,5; Ye, Yi2,5; Tang, Ying2,5; Wu, Qibiao2,5 |
| 刊名 | JOURNAL OF CLINICAL INVESTIGATION
 |
| 出版日期 | 2019 |
| 卷号 | 129期号:3页码:972-987 |
| ISSN号 | 0021-9738 |
| DOI | 10.1172/JCI122779 |
| 文献子类 | Article |
| 英文摘要 | Metastasis is the dominant cause of patient death in small-cell lung cancer (SCLC), and a better understanding of the molecular mechanisms underlying SCLC metastasis may potentially improve clinical treatment. Through genome-scale screening for key regulators of mouse Rb1(-/-) Trp53(-/-) SCLC metastasis using the pooled CRISPR/Cas9 library, we identified Cullin5 (CUL5) and suppressor of cytokine signaling 3 (SOCS3), two components of the Cullin-RING E3 ubiquitin ligase complex, as top candidates. Mechanistically, the deficiency of CUL5 or SOCS3 disrupted the functional formation of the E3 ligase complex and prevented the degradation of integrin beta 1, which stabilized integrin beta 1 and activated downstream focal adhesion kinase/SRC (FAK/SRC) signaling and eventually drove SCLC metastasis. Low expression levels of CUL5 and SOCS3 were significantly associated with high integrin beta 1 levels and poor prognosis in a large cohort of 128 clinical patients with SCLC. Moreover, the CUL5-deficient SCLCs were vulnerable to the treatment of the FDA-approved SRC inhibitor dasatinib. Collectively, this work identifies the essential role of CUL5- and SOCS3-mediated integrin beta 1 turnover in controlling SCLC metastasis, which might have therapeutic implications. |
| 学科主题 | Research & Experimental Medicine |
| WOS关键词 | DRIVES PROTEASOMAL DEGRADATION ; POOR PROGNOSTIC-FACTOR ; SOCS-BOX ; MOUSE MODEL ; CUL5-RBX2 MODULES ; EXPRESSION ; GROWTH ; SRC ; MYC ; CARCINOMA |
| 语种 | 英语 |
| WOS记录号 | WOS:000460125800013 |
| 出版者 | AMER SOC CLINICAL INVESTIGATION INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/494]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China; 2.Univ Chinese Acad Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Inst Hlth Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China; 4.NYU Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA, 5.Chinese Acad Sci, Innovat Ctr Cell Signaling Network, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,State Key Lab Cel, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 6.Zhejiang Canc Hosp, Dept Pathol, Hangzhou, Zhejiang, Peoples R China; 7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhao, Gaoxiang,Gong, Liyan,Jin, Yujuan,et al. Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin beta 1[J]. JOURNAL OF CLINICAL INVESTIGATION,2019,129(3):972-987. |
| APA | Zhao, Gaoxiang.,Gong, Liyan.,Jin, Yujuan.,Guo, Chenchen.,Yue, Meiting.,...&,.(2019).Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin beta 1.JOURNAL OF CLINICAL INVESTIGATION,129(3),972-987. |
| MLA | Zhao, Gaoxiang,et al."Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin beta 1".JOURNAL OF CLINICAL INVESTIGATION 129.3(2019):972-987. |
入库方式： OAI收割
来源：上海营养与健康研究所
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