Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia
Model organisms
Chemical Biology & High Throughput
0301 basic medicine
570
Human Biology & Physiology
0303 health sciences
Stem Cells
Genome Integrity & Repair
610
Gene Expression
Cell Biology
Tumour Biology
Imaging
3. Good health
03 medical and health sciences
Phenotype
Neoplasms
Mutation
Humans
Cell Cycle & Chromosomes
Genetics & Genomics
Computational & Systems Biology
DOI:
10.1016/j.ccell.2022.10.002
Publication Date:
2022-11-03T14:26:45Z
AUTHORS (15)
ABSTRACT
The evolution of established cancers is driven by selection cells with enhanced fitness. Subclonal mutations in numerous epigenetic regulator genes are common across cancer types, yet their functional impact has been unclear. Here, we show that disruption the regulatory network increases tolerance to unfavorable environments experienced within growing tumors promoting emergence stress-resistant subpopulations. Disruption control does not promote genetically defined subclones or favor a phenotypic switch response environmental changes. Instead, it prevents from mounting an efficient stress via modulation global transcriptional activity. This "transcriptional numbness" lowers probability cell death at early stages, increasing chance long-term adaptation population level. Our findings provide mechanistic explanation for widespread subclonal epigenetic-related and uncover inertia as cellular trait drives subclone expansion.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (96)
CITATIONS (35)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....