| Accession |
PRJCA018457 |
| Title |
An integrated molecular and cellular model of lung squamous transition mediating EGFR TKI resistance highlights RAPGEF3 as therapeutic targets |
| Relevance |
Medical |
| Data types |
Epigenomics
Transcriptome or Gene expression
Single cell sequencing
|
| Organisms |
Homo sapiens
|
| Description |
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. |
| Sample scope |
Synthetic |
| Release date |
2023-07-19 |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| No funding support
|
|
|
|
|
|
| Submitter |
Shijie
Tang (tangshijie6@sibcb.ac.cn)
|
| Organization |
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences |
| Submission date |
2023-07-19 |
