We further observed that, while elevated KLF4 enhances colony formation in MDA‐MB‐231, MCF10A as well as U2OS cells, the KLF4 PARylation mutant loses its capability to promote tumor cell colony formation (Fig 7D–F), suggesting KLF4 PARylation plays a critical role in regulating DNA damage response‐associated cell death, tumor initiation, and tumor progression. Here, KLF4 is linked to neoplasm.