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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 01, 2023 |
| Title |
Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma [RNA-seq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing Kras induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD.
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| Overall design |
Normal lung alveolar type 2 cells and tumor cells of KP tumors were isolated from KP mouse model using flurescence-activated cell soring and analyzed by scRNAseq or bulk RNAseq.
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| Contributor(s) |
Li Z, Zhuang X, Pan C, Joost S, Torborg S, Tammela T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Oct 28, 2023 |
| Last update date |
Nov 01, 2023 |
| Contact name |
ZHUXUAN LI |
| E-mail(s) |
liz3@mskcc.org
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| Phone |
6467043994
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| Organization name |
Memorial Sloan Kettering Cancer Center
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| Department |
Cancer Biology and Genetics
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| Lab |
Tuomas Tammela
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| Street address |
417 E 68th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (15)
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| GSM7869575 |
lung tumor, vehicle, rep 1 |
| GSM7869576 |
lung tumor, vehicle, rep 2 |
| GSM7869577 |
lung tumor, vehicle, rep 3 |
| GSM7869578 |
lung tumor, vehicle, rep 4 |
| GSM7869579 |
lung tumor, cisplatin, rep 4 |
| GSM7869580 |
lung tumor, cisplatin, rep 5 |
| GSM7869581 |
PDX, vehicle, rep 1 |
| GSM7869582 |
PDX, adagrasib, rep 1 |
| GSM7869583 |
PDX, vehicle, rep 2 |
| GSM7869584 |
PDX, adagrasib, rep 2 |
| GSM7869585 |
PDX, vehicle, rep 3 |
| GSM7869586 |
PDX, adagrasib, rep 3 |
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| This SubSeries is part of SuperSeries: |
| GSE246482 |
Alveolar differentiation drives resistance to KRAS inhibition in lung adenocarcinoma |
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| Relations |
| BioProject |
PRJNA1033181 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246480_Cisplatin_dds.Rdata.gz |
8.4 Mb |
(ftp)(http) |
RDATA |
| GSE246480_PDX_CountMatrix_dds.Rdata.gz |
10.1 Mb |
(ftp)(http) |
RDATA |
SRA Run Selector |
| Raw data are available in SRA |
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