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| Status |
Public on Jun 17, 2024 |
| Title |
Genomic heterogeneity drives mechanical adaptation in human tumor cells [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The progression of many solid tumors is accompanied by temporal and spatial changes in the stiffness of the extracellular matrix (ECM). Cancer cells adapt to soft and stiff ECM through mechanisms that are not fully understood. In particular, it is well known that there is significant genetic heterogeneity from cell to cell in tumors, but how ECM stiffness as a parameter might interact with that genetic variation is not known. Here, we used the method of experimental evolution to study response of genetically variable and clonal tumor cell populations to ECM stiffness. Cell fitness increased on soft ECM over a period of several weeks in genetically variable but not clonal populations. DNA barcode-enabled clonal tracking revealed that sustained culture on soft ECM selects for a few genetic variants. These data provide the first evidence that ECM stiffness exerts natural selection on genetically variable tumor populations. Genome-wide analysis including RNA-seq, ATAC-seq and DNA methylation profiling reveal substantial differences in gene expression between selected populations and ancestral cells which are partially explained by epigenetic modifications. Soft-selected cells are highly migratory with enriched oncogenic signatures and exhibit highly unusual behaviors like spreading and traction force generation on ECMs as soft as 1 kPa. Cell spreading is the directly selected trait but not levels of integrins or adhesion proteins like talin. Overall, these data show that ECM stiffness in solid tumors may drive malignant behaviors through evolution by natural selection.
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| Overall design |
To explore the mechanism underlying cell evolution on soft ECM, we performed whole genome transcriptome sequencing (RNA-seq).
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| Contributor(s) |
Wang T, Sawhney S, Morgan D, Bennett RL, Rashmi R, Estecio MR, Brock A, Singh I, Baer CF, Licht JD, Lele TP |
| Citation(s) |
39302966 |
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| Submission date |
Feb 14, 2024 |
| Last update date |
Sep 24, 2024 |
| Contact name |
Ting-Ching Wang |
| E-mail(s) |
tcwang@tamu.edu
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| Phone |
979-739-4958
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| Organization name |
Texas A&M University
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| Street address |
101 Bizzell St
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| City |
College Station |
| ZIP/Postal code |
77843 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (16)
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| GSM8081354 |
MDA-MB-231, ancestral on soft, rep 1 (RNA-seq) |
| GSM8081355 |
MDA-MB-231, ancestral on soft, rep 2 (RNA-seq) |
| GSM8081356 |
MDA-MB-231, ancestral on soft, rep 3 (RNA-seq) |
| GSM8081357 |
MDA-MB-231, ancestral on soft, rep 4 (RNA-seq) |
| GSM8081358 |
MDA-MB-231, ancestral on stiff, rep 1 (RNA-seq) |
| GSM8081359 |
MDA-MB-231, ancestral on stiff, rep 2 (RNA-seq) |
| GSM8081360 |
MDA-MB-231, ancestral on stiff, rep 3 (RNA-seq) |
| GSM8081361 |
MDA-MB-231, ancestral on stiff, rep 4 (RNA-seq) |
| GSM8081362 |
MDA-MB-231, selected on soft, rep 1 (RNA-seq) |
| GSM8081363 |
MDA-MB-231, selected on soft, rep 2 (RNA-seq) |
| GSM8081364 |
MDA-MB-231, selected on soft, rep 3 (RNA-seq) |
| GSM8081365 |
MDA-MB-231, selected on soft, rep 4 (RNA-seq) |
| GSM8081366 |
MDA-MB-231, selected on stiff, rep 1 (RNA-seq) |
| GSM8081367 |
MDA-MB-231, selected on stiff, rep 2 (RNA-seq) |
| GSM8081368 |
MDA-MB-231, selected on stiff, rep 3 (RNA-seq) |
| GSM8081369 |
MDA-MB-231, selected on stiff, rep 4 (RNA-seq) |
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| Relations |
| BioProject |
PRJNA1076641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255829_fpkm_rna.txt.gz |
2.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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