|
| Status |
Public on Mar 25, 2019 |
| Title |
Flura-seq identifies organ-specific adaptations in metastasis-initiating cells |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Metastasis-initiating cells dynamically adapt to the distinct microenvironments of different organs, but these early adaptations are poorly understood due to the limited sensitivity of in situ transcriptomics. We developed fluorouracil-labeled RNA sequencing (Flura-seq) for in situ analysis with unprecedented sensitivity. Flura-seq utilizes cytosine deaminase (CD) to convert fluorocytosine to fluorouracil, covalently labeling nascent RNA for purification and sequencing. Flura-seq revealed that breast cancer micrometastases in lung and brain exhibit unique, reversible gene signatures depending on the microenvironment. Specifically, the mitochondrial electron transport Complex I and the NRF2-driven antioxidant programs were induced in oxygen-rich pulmonary micrometastases, compared to mammary tumors or brain micrometastases. Loss of Complex I activity, and antioxidant supplementation potentiated pulmonary metastatic growth. We confirm lung metastasis-specific NRF2 overexpression in clinical samples, thus validating Flura-seq’s utility in identifying clinically actionable microenvironmental adaptations in early metastasis. The sensitivity, robustness and economy of Flura-seq are broadly applicable beyond cancer research.
|
| |
|
| Overall design |
Examination of 5-FU labeled RNAs in cancer cells present in different organs
|
| |
|
| Contributor(s) |
Basnet H, Tian L, Massagué J |
| Citation(s) |
30912515 |
| Submission date |
Aug 22, 2018 |
| Last update date |
Apr 09, 2019 |
| Contact name |
Lin Tian |
| E-mail(s) |
tianl1@mskcc.org
|
| Phone |
6468882063
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Department |
Cancer Biology & Genetics Program
|
| Lab |
Joan Massagué
|
| Street address |
Mortimer B. Zuckerman Research Center, 417 East 68th Street
|
| City |
New York City |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16512 |
Illumina HiSeq 2000 (Homo sapiens; Mus musculus) |
|
| Samples (27)
|
|
| Relations |
| BioProject |
PRJNA487361 |
| SRA |
SRP158622 |
Less...
More...