| |||||||
ShanghaiTech University Knowledge Management System
| Functional Phosphoproteomics in Cancer Chemoresistance Using CRISPR-Mediated Base Editors | |
| 2022-10-25 | |
| 发表期刊 | ADVANCED SCIENCE (IF:14.3[JCR-2023],16.3[5-Year]) |
| EISSN | 2198-3844 |
| 发表状态 | 已发表 |
| DOI | 10.1002/advs.202200717 |
| 摘要 | Selective inhibition of targeted protein kinases is an effective therapeutic approach for treatment of human malignancies, which interferes phosphorylation of cellular substrates. However, a drug-imposed selection creates pressures for tumor cells to acquire chemoresistance-conferring mutations or activating alternative pathways, which can bypass the inhibitory effects of kinase inhibitors. Thus, identifying downstream phospho-substrates conferring drug resistance is of great importance for developing poly-pharmacological and targeted therapies. To identify functional phosphorylation sites involved in 5-fluorouracil (5-FU) resistance during its treatment of colorectal cancer cells, CRISPR-mediated cytosine base editor (CBE) and adenine base editor (ABE) are utilized for functional screens by mutating phosphorylated amino acids with two libraries specifically targeting 7779 and 10 149 phosphorylation sites. Among the top enriched gRNAs-induced gain-of-function mutants, the target genes are involved in cell cycle and post-translational covalent modifications. Moreover, several substrates of RSK2 and PAK4 kinases are discovered as main effectors in responding to 5-FU chemotherapy, and combinational treatment of colorectal cancer cells with 5-FU and RSK2 inhibitor or PAK4 inhibitor can largely inhibit cell growth and enhance cell apoptosis through a RSK2/TP53BP1/gamma-H2AX phosphorylation signaling axis. It is proposed that this screen approach can be used for functional phosphoproteomics in chemotherapy of various human diseases. |
| 关键词 | 5-fluorouracil (5-FU) base editors functional phosphoproteomics RSK2 screen |
| URL | 查看原文 |
| 收录类别 | SCI ; EI ; SCIE |
| 语种 | 英语 |
| 资助项目 | Excellent Youth Foundation of Guangdong Scientific Committee[2020B1515020018] ; National Key Research and Development Program["2021YFA0804702","2018YFC1004700"] ; [17JC1420103] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| WOS类目 | Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary |
| WOS记录号 | WOS:000847934200001 |
| 出版者 | WILEY |
| 引用统计 | 正在获取...
|
| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/226369 |
| 专题 | 生命科学与技术学院_硕士生 生命科学与技术学院_PI研究组_黄行许组 生命科学与技术学院_博士生 |
| 通讯作者 | Huang, Xingxu; Qiao, Yunbo |
| 作者单位 | 1.Zhejiang Univ, Sch Med, Zhejiang Prov Key Lab Pancreat Dis, Affiliated Hosp 1, Hangzhou 310029, Peoples R China 2.Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou 310029, Peoples R China 3.Zhejiang Lab, Hangzhou 311121, Zhejiang, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Shanghai 200125, Peoples R China 5.Shanghai Inst Precis Med, Shanghai 200125, Peoples R China 6.Guangzhou Univ, Sch Life Sci, Precise Genome Engn Ctr, Guangzhou 510006, Peoples R China 7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China |
| 通讯作者单位 | 生命科学与技术学院 |
| 推荐引用方式 GB/T 7714 | Li, Jianan,Lin, Jianxiang,Huang, Shisheng,et al. Functional Phosphoproteomics in Cancer Chemoresistance Using CRISPR-Mediated Base Editors[J]. ADVANCED SCIENCE,2022. |
| APA | Li, Jianan.,Lin, Jianxiang.,Huang, Shisheng.,Li, Min.,Yu, Wenxia.,...&Qiao, Yunbo.(2022).Functional Phosphoproteomics in Cancer Chemoresistance Using CRISPR-Mediated Base Editors.ADVANCED SCIENCE. |
| MLA | Li, Jianan,et al."Functional Phosphoproteomics in Cancer Chemoresistance Using CRISPR-Mediated Base Editors".ADVANCED SCIENCE (2022). |
| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
修改评论
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。