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Accelerated senescence of cancer stem cells: A failure to thrive or a route to survival?

Accelerated senescence of cancer stem cells: A failure to thrive or a route to survival?
Accelerated senescence of cancer stem cells: A failure to thrive or a route to survival?
Accelerated senescence of cancer stem cells (CSCs) represents an adaptive response allowing withstand cell death. TP53, the pivotal tumor suppressor plays an important role in this process by inducing a prolonged dual state with senescence and self-renewal as potential outcomes. Molecularly, this is achieved by activating both OCT4A (POU5F1) and p21CIP1. OCT4A suppresses the excessive activity of p21 preventing the immediate precipitation of apoptosis or terminal senescence. It persists as long as sufficient cellular energy remains; generated through autophagy, itself sequestrating p16INK4A in the cytoplasm. As such, autophagic capacity is the bottleneck of these TP53-dependent senescence reversal processes, as well terminal senescence will follow if DNA damage is not ultimately repaired. In TP53 mutants the CSC-like state is boosted by stressed cells overcoming the tetraploidy barrier. These cells acquire additional DNA repair capacity through mitotic slippage and entrance to a sequence of ploidy cycles, allowing repair and sorting DNA damage, ultimately facilitating the genesis of mitotically competent daughter cells following final depolyploidisation. Again, autophagy is required to fuel this process. More detailed knowledge of these arcane processes anticipates the provision of anti-cancer drug targets, such as AURORA B kinase and Survivin, which ensure mitotic slippage and the continuity of ploidy cycles.
387 - 398
INTECH
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
Salmina, Kristine
00a98b4d-8de8-4e78-99f7-a8834851d209
Cragg, Mark Steven
ec97f80e-f3c8-49b7-a960-20dff648b78c
Dorszewska, Jolanta
Kozubski, Wojciech
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
Salmina, Kristine
00a98b4d-8de8-4e78-99f7-a8834851d209
Cragg, Mark Steven
ec97f80e-f3c8-49b7-a960-20dff648b78c
Dorszewska, Jolanta
Kozubski, Wojciech

Erenpreisa, Jekaterina, Salmina, Kristine and Cragg, Mark Steven (2017) Accelerated senescence of cancer stem cells: A failure to thrive or a route to survival? In, Dorszewska, Jolanta and Kozubski, Wojciech (eds.) Senescence: Physiology or Pathology. INTECH, 387 - 398. (doi:10.5772/intechopen.68582).

Record type: Book Section

Abstract

Accelerated senescence of cancer stem cells (CSCs) represents an adaptive response allowing withstand cell death. TP53, the pivotal tumor suppressor plays an important role in this process by inducing a prolonged dual state with senescence and self-renewal as potential outcomes. Molecularly, this is achieved by activating both OCT4A (POU5F1) and p21CIP1. OCT4A suppresses the excessive activity of p21 preventing the immediate precipitation of apoptosis or terminal senescence. It persists as long as sufficient cellular energy remains; generated through autophagy, itself sequestrating p16INK4A in the cytoplasm. As such, autophagic capacity is the bottleneck of these TP53-dependent senescence reversal processes, as well terminal senescence will follow if DNA damage is not ultimately repaired. In TP53 mutants the CSC-like state is boosted by stressed cells overcoming the tetraploidy barrier. These cells acquire additional DNA repair capacity through mitotic slippage and entrance to a sequence of ploidy cycles, allowing repair and sorting DNA damage, ultimately facilitating the genesis of mitotically competent daughter cells following final depolyploidisation. Again, autophagy is required to fuel this process. More detailed knowledge of these arcane processes anticipates the provision of anti-cancer drug targets, such as AURORA B kinase and Survivin, which ensure mitotic slippage and the continuity of ploidy cycles.

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More information

e-pub ahead of print date: 30 August 2017
Published date: 30 August 2017

Identifiers

Local EPrints ID: 426688
URI: http://eprints.soton.ac.uk/id/eprint/426688
PURE UUID: 63b9e3cd-4087-42f6-abdf-54637f8ad3db
ORCID for Mark Steven Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 10 Dec 2018 17:31
Last modified: 10 Nov 2021 02:53

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Contributors

Author: Jekaterina Erenpreisa
Author: Kristine Salmina
Editor: Jolanta Dorszewska
Editor: Wojciech Kozubski

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