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CENP-A overexpression drives distinct cell fates depending on p53 status

Abstract : Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays and single-cell RNA-sequencing over time, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. But, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential precursor for tumour cell invasion and metastasis. Thus, CENP-A overexpression drives distinct cell fates depending on p53 status, with important implications for tumour evolution.
Keywords : Cancer Biology
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Preprints, Working Papers, ...
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https://hal.archives-ouvertes.fr/hal-03041329
Contributor : Geneviève Almouzni Connect in order to contact the contributor
Submitted on : Friday, December 4, 2020 - 7:53:20 PM
Last modification on : Tuesday, October 19, 2021 - 11:00:29 AM

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Daniel Jeffery, Katrina Podsypanina, Alberto Gatto, Rebeca Ponce Landete, Lorraine Bonneville, et al.. CENP-A overexpression drives distinct cell fates depending on p53 status. 2020. ⟨hal-03041329⟩

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