The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α

摘要: Deviating from the normal karyotype dramatically changes gene dosage, in turn decreasing robustness of biological networks. Consequently, aneuploidy is poorly tolerated by somatic cells and acts as a barrier to transformation. Paradoxically, however, heterogeneity drives tumor evolution emergence therapeutic drug resistance. To better understand how cancer tolerate aneuploidy, we focused on p38 stress response kinase. We show here that p38-deficient upregulate glycolysis avoid post-mitotic apoptosis, leading aneuploid subclones. also deficiency upregulates hypoxia-inducible transcription factor Hif-1 alpha inhibiting restores apoptosis p38-deficent cells. Because hypoxia are both barriers progression, ability promote cell survival following chromosome missegregation raises possibility tolerance coevolves with adaptation hypoxia.