| 项目编号 |
PRJCA018457 |
| 项目标题 |
An integrated molecular and cellular model of lung squamous transition mediating EGFR TKI resistance highlights RAPGEF3 as therapeutic targets |
| 涉及领域 |
Medical |
| 数据类型 |
Epigenomics
Transcriptome or Gene expression
Single cell sequencing
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
We here demonstrate that squamous transition occurs concomitantly with the acquisition of TKI resistance in xenograft tumors derived from EGFR-mutant PC9 cell. Perturbation of squamous transition via DNp63 overexpression or knockout results in significant changes of TKI responses, indicating a direct causality between squamous transition and TKI resistance. Integrative RNA-seq and ATAC-seq analyses along with functional studies reveal that FOXA1 plays a pivotal role in maintaining adenomatous lineage and contributing to TKI sensitivity. We further find that co-expression of FOXM1 and knockout of FOXA1 fully recapitulates squamous transition and TKI resistance in PC9 xenografts and patient-derived xenograft (PDX) models. |
| 样品范围 |
Synthetic |
| 发布日期 |
2023-07-19 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
|
|
Integrative study of lung cancer adeno-to-squamous transition in EGFR TKI resistance identifies RAPGEF3 as a therapeutic target
|
National Science Review
|
10.1093/nsr/nwae392
|
2024
|
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| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| No funding support
|
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|
|
|
|
| 提交者 |
Shijie
Tang (tangshijie6@sibcb.ac.cn)
|
| 提交单位 |
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences |
| 提交日期 |
2023-07-19 |
