aneuploidAneuploidy and chromosomal instability demonstrate contrasting effects depending on cellular context: while increased aneuploidy can drive spontaneous tumor formation in aged animals, it simultaneously prevents tumorigenesis in chemically or genetically induced tumor models. This reveals that the same genomic instability phenotype can function both as an oncogenic driver and as a tumor suppressor depending on the tumor initiation mechanism. [@weaver_aneuploidy_2007]
Definitions
- aneuploidaneuploidy
- chromosomal instability
- tumorigenesis
- oncogenic
- tumor suppressor
- chemical carcinogens
- genetic alterations
- spontaneous tumor formation
- models
- phenotype
Synthesis
Research establishes that aneuploidy plays paradoxical roles in cancer development, acting both as a tumor promoter and suppressor depending on context. Studies demonstrate that increased aneuploidy drives spontaneous tumor formation in aged animals, supporting the oncogenic potential of chromosomal instability, yet this same instability acts as a more effective inhibitor than initiator of tumorigenesis when tumors are induced by chemical carcinogens or genetic alterations. Mechanistically, aneuploid cells that successfully transform into tumors do so by inactivating Stat1 signaling while activating Myc, a combination that suppresses the immune cell infiltration normally triggered by chromosomal instability and allows aneuploid cells to evade immune surveillance. The dual nature of aneuploidy appears to depend on whether cells can overcome the fitness costs imposed by chromosomal imbalance, with the tumor-suppressive effects dominating in contexts where cells lack the adaptive mechanisms to tolerate ongoing chromosome missegregation.
Related
- Stat1 inactivation mechanism is conserved between mouse and human aneuploid cancers
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
- Multipolar divisions are rare and typically produce inviable progeny
- Different aneuploid cells share common fitness-related traits
- Aneuploidy impairs cell cycle progression in haploid yeast
- Extra chromosome genes drive aneuploid phenotypes through imbalanced protein composition
- Aneuploidy increases spontaneous tumor formation in aged animals
- Increased aneuploidy inhibits chemically and genetically induced tumorigenesis
- Aneuploid tumors inactivate Stat1 signaling with increased Myc activity
- Extra centrosomes correlate with chromosomal instability in tumors
- Stat1 loss combined with Myc activation alleviates CIN-induced immune infiltration
- CIN exists independently of classic mitotic defects in most cells
- Single-cell sequencing reveals karyotype heterogeneity in lymphomas
- CIN causality toward aneuploidy was previously unanswered
- CENP-E reduction generates aneuploidy and chromosomal instability
- Missegregation alone insufficient for aneuploid cell propagation