Nature Communications, Published online: 21 June 2026; doi:10.1038/s41467-026-74702-9 A genome wide screen reveals down-regulating the Wnt, Hippo, Tpr53, PIDDosome, ciliary biogenesis, or autophagy pathways overcomes inhibitory effects of PLK4-mediated centrosome amplification on cell proliferation. Depletion of tumor suppressor, ARHGAP15, activates autophagy to reduce centrosomes. ARHGAP15 is opposed by ARHGEF2, which is activated by centriolar protein CEP170 to generate RAC1-GTP and promote au