The mechanism by which aneuploid tumors inactivate Stat1 signaling to suppress immune infiltration is preserved and functional in human aneuploid cancers, indicating that this pathway represents a conserved evolutionary solution for chromosomally unstable cells to achieve malignant transformation. [@schubert_cancer_2021]
Definitions
- aneuploidaneuploidy
- chromosomal instability
- malignancy
- stat1 inactivation
- stat1 signaling
- tumor
- aneuploid
- tumors
- immune infiltration
Synthesis
The inactivation of Stat1 signaling in aneuploid tumors represents a conserved evolutionary strategy across both mouse models and human cancers to evade the immune surveillance that chromosomal instability normally triggers. This mechanism is consistently coupled with increased Myc activity, forming a dual adaptation that allows chromosomally unstable tumor cells to suppress the immune cell infiltration that would otherwise limit their proliferation and malignancy. While the mechanistic relationship between Stat1 loss, Myc activation, and immune evasion in aneuploid cancers is well-established across species, what remains less clear is whether this represents the only viable pathway for aneuploid cells to overcome immune-mediated fitness costs, given that p53 loss—despite being common in many cancers—is notably not enriched in chromosomally unstable tumors specifically.
Related
- Mps1 truncation-induced CIN generates convergent recurrent chromosome gains
- Chromosomal instability promotes immune cell infiltration into tumors
- Subclonal driver events determine therapy response and tumor evolution
- Hypoxia-related transcriptional programs are variably expressed in glioblastoma cells
- Multipolar divisions are rare and typically produce inviable progeny
- Aneuploid cancers inactivate Stat1 to circumvent immune surveillance
- 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
- Aneuploidy exhibits dual roles as oncogenic and tumor-suppressive
- CIN causality toward aneuploidy was previously unanswered
- p53 loss is common but not enriched in chromosomally unstable tumors
- CENP-E reduction generates aneuploidy and chromosomal instability
- Missegregation alone insufficient for aneuploid cell propagation
- Tumors contain multiple subclones with spatial and temporal heterogeneity