Ki-67 supports global gene expression programmes driving tumourigenesis

Mrouj, K.; Singh, P.; Sobecki, M.; Dubra, G.; Al Ghoul, E.; Aznar, A. B.; prieto, S.; Vincent, C.; Pirot, N.; Bernex, F.; Bordignon, B.; Hassen-Khodja, C.; Pouzolles, M.; Zimmerman, V.; Dardalhon, V.; Villalba, M.; Krasinska, L.; Fisher, D.

doi:10.1101/712380

bioRxiv · 10.1101/712380

Ki-67 supports global gene expression programmes driving tumourigenesis

Mrouj, K.·Singh, P.·Sobecki, M.·Dubra, G.·Al Ghoul, E.·Aznar, A. B.·prieto, S.·Vincent, C.·Pirot, N.·Bernex, F.·Bordignon, B.·Hassen-Khodja, C.·Pouzolles, M.·Zimmerman, V.·Dardalhon, V.·Villalba, M.·Krasinska, L.·Fisher, D.

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Abstract

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.

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Mrouj, K., Singh, P., Sobecki, M., Dubra, G., Al Ghoul, E., Aznar, A. B., prieto, S., Vincent, C., Pirot, N., Bernex, F., Bordignon, B., Hassen-Khodja, C., Pouzolles, M., Zimmerman, V., Dardalhon, V., Villalba, M., Krasinska, L., Fisher, D.. 2019-07-24. Ki-67 supports global gene expression programmes driving tumourigenesis. https://doi.org/10.1101/712380

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