Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis

Significance Ki-67 is a nuclear protein present in all proliferating vertebrate cells and is widely used as a marker in clinical cancer histopathology. However, its cellular functions have remained largely mysterious, and whether it plays any roles in cancer was unknown. In this work, we show genetically that Ki-67 is not required for cell proliferation in tumors, but it is required for all stages of carcinogenesis. The effects on cell transformation, tumor growth, metastasis, and drug sensitivity correlate with genome-scale changes in gene expression that modify cellular programs implicated in cancer. Thus, Ki-67 expression is advantageous for cancer cells, but it comes with an Achilles’ heel: it makes them more visible to the immune system.