PT  - JOURNAL ARTICLE
AU  - K. Mrouj
AU  - P. Singh
AU  - M. Sobecki
AU  - G. Dubra
AU  - E. Al Ghoul
AU  - A. Aznar
AU  - S. Prieto
AU  - N. Pirot
AU  - F. Bernex
AU  - B. Bordignon
AU  - C. Hassen-Khodja
AU  - M. Pouzolles
AU  - V. Zimmerman
AU  - V. Dardalhon
AU  - L. Krasinska
AU  - D. Fisher
TI  - Ki-67 promotes sequential stages of tumourigenesis by enabling cellular plasticity
AID  - 10.1101/712380
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 712380
4099  - http://biorxiv.org/content/early/2019/12/13/712380.short
4100  - http://biorxiv.org/content/early/2019/12/13/712380.full
AB  - Recent studies have shown that the cell proliferation antigen Ki-67 is not required for cell proliferation. Here, we demonstrate that Ki-67 enables implementation of transcriptional programmes conferring cellular plasticity, and is required for each step of tumour initiation, growth and metastasis. Ki-67 knockout causes global transcriptome remodelling, which, in mammary carcinoma cells, inhibits the epithelial-mesenchymal transition in a polycomb-repressive complex 2-dependent manner. This results in suppression of stem cell characteristics and sensitisation to various drug classes. Cancer cells lacking Ki-67 proliferate normally in vivo, but tumour growth is inhibited due to disrupted angiogenesis, and metastasis is abrogated. Finally, mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumourigenesis. Thus, Ki-67, which is expressed in all proliferating cancer cells, confers the plasticity required for different steps of carcinogenesis.