Tetraploid cancer cell precursors

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Tetraploid cancer cell precursors in ovarian carcinoma

The rapid accumulation of signaling and repair factors in the vicinity of DNA lesions is an integral part of the cellular DNA damage response (DDR) to DNA double-strand breaks (DSBs).1,2 This is initiated by posttranslational modifications of core histones, to which various effector proteins bind. The priming modification is ATM-mediated phosphorylation of histone H2AX at Ser-139 (γ-H2AX), a ma...

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Apoptosis regulation in tetraploid cancer cells.

Tetraploidy can result in cancer-associated aneuploidy. As shown here, freshly generated tetraploid cells arising due to mitotic slippage or failed cytokinesis are prone to undergo Bax-dependent mitochondrial membrane permeabilization and subsequent apoptosis. Knockout of Bax or overexpression of Bcl-2 facilitated the survival of tetraploid cells at least as efficiently as the p53 or p21 knocko...

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Epithelial cell identity in hyperplastic precursors of breast cancer

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Failure of cell cleavage induces senescence in tetraploid primary cells

Tetraploidy can arise from various mitotic or cleavage defects in mammalian cells, and inheritance of multiple centrosomes induces aneuploidy when tetraploid cells continue to cycle. Arrest of the tetraploid cell cycle is therefore potentially a critical cellular control. We report here that primary rat embryo fibroblasts (REF52) and human foreskin fibroblasts become senescent in tetraploid G1 ...

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Novel Roles for P53 in the Genesis and Targeting of Tetraploid Cancer Cells

Tetraploid (4N) cells are considered important in cancer because they can display increased tumorigenicity, resistance to conventional therapies, and are believed to be precursors to whole chromosome aneuploidy. It is therefore important to determine how tetraploid cancer cells arise, and how to target them. P53 is a tumor suppressor protein and key regulator of tetraploidy. As part of the "tet...

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ژورنال

عنوان ژورنال: Nature Reviews Molecular Cell Biology

سال: 2010

ISSN: 1471-0072,1471-0080

DOI: 10.1038/nrm2924