SMARCB1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (BRG1-associated factor 47) (BAF47) (Integrase interactor 1 protein) (SNF5 homolog) (hSNF5) [BAF47] [INI1] [SNF5L1]
Publications[править]
Senescence is a proliferation arrest that can result from a variety of stresses. Cancer cells can also undergo senescence, but the stresses that provoke cancer cells to undergo senescence are unclear. Here, we use both functional genetic and compound screens in cancer cells harboring a reporter that is activated during senescence to find targets that induce senescence. We show that suppression of the SWI/SNF component SMARCB1 induces senescence in melanoma through strong activation of the MAP kinase pathway. From the compound screen, we identified multiple aurora kinase inhibitors as potent inducers of senescence in RAS mutant lung cancer. Senescent melanoma and lung cancer cells acquire sensitivity to the BCL2 family inhibitor ABT263. We propose a one-two punch approach for the treatment of cancer in which a drug is first used to induce senescence in cancer cells and a second drug is then used to kill senescent cancer cells.
MeSH Terms
- Aurora Kinases
- CRISPR-Cas Systems
- Cell Line, Tumor
- Cellular Senescence
- Down-Regulation
- ErbB Receptors
- Gene Knockout Techniques
- Genes, Reporter
- Genetic Testing
- Green Fluorescent Proteins
- High-Throughput Screening Assays
- Humans
- Melanoma
- Neoplasms
- Oncogenes
- Protein Kinase Inhibitors
- SMARCB1 Protein
- SOXE Transcription Factors
Keywords
- SWI/SNF
- aurora kinase
- compound screen
- genetic screens
- miR146
- senescence
- senolysis