Pluripotency Stemness and Cancer: More Questions than Answers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F22%3A10446481" target="_blank" >RIV/00216208:11140/22:10446481 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1007/5584_2021_663" target="_blank" >https://doi.org/10.1007/5584_2021_663</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/5584_2021_663" target="_blank" >10.1007/5584_2021_663</a>

Result language

angličtina

Original language name

Pluripotency Stemness and Cancer: More Questions than Answers

Original language description

Embryonic stem cells and induced pluripotent stem cells provided us with fascinating new knowledge in recent years. Mechanistic insight into intricate regulatory circuitry governing pluripotency stemness and disclosing parallels between pluripotency stemness and cancer instigated numerous studies focusing on roles of pluripotency transcription factors, including Oct4, Sox2, Klf4, Nanog, Sall4 and Tfcp2L1, in cancer. Although generally well substantiated as tumour-promoting factors, oncogenic roles of pluripotency transcription factors and their clinical impacts are revealing themselves as increasingly complex. In certain tumours, both Oct4 and Sox2 behave as genuine oncogenes, and reporter genes driven by composite regulatory elements jointly recognized by both the factors can identify stem-like cells in a proportion of tumours. On the other hand, cancer stem cells seem to be biologically very heterogeneous both among different tumour types and among and even within individual tumours. Pluripotency transcription factors are certainly implicated in cancer stemness, but do not seem to encompass its entire spectrum. Certain cancer stem cells maintain their stemness by biological mechanisms completely different from pluripotency stemness, sometimes even by engaging signalling pathways that promote differentiation of pluripotent stem cells. Moreover, while these signalling pathways may well be antithetical to stemness in pluripotent stem cells, they may cooperate with pluripotency factors in cancer stem cells - a paradigmatic example is provided by the MAPK-AP-1 pathway. Unexpectedly, forced expression of pluripotency transcription factors in cancer cells frequently results in loss of their tumour-initiating ability, their phenotypic reversion and partial epigenetic normalization. Besides the very different signalling contexts operating in pluripotent and cancer stem cells, respectively, the pronounced dose dependency of reprogramming pluripotency factors may also contribute to the frequent loss of tumorigenicity observed in induced pluripotent cancer cells. Finally, contradictory cell-autonomous and non-cell-autonomous effects of various signalling molecules operate during pluripotency (cancer) reprogramming. The effects of pluripotency transcription factors in cancer are thus best explained within the concept of cancer stem cell heterogeneity.

Czech name

—

Czech description

—

Type

C - Chapter in a specialist book

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/GA17-17636S" target="_blank" >GA17-17636S: Identification of new prognostic markers and therapeutic target molecules in soft tissue sarcoma</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Book/collection name

Cell Biology and Translational Medicine, Volume 15

ISBN

978-3-031-02377-4

Number of pages of the result

24

Pages from-to

77-100

Number of pages of the book

205

Publisher name

Springer

Place of publication

Cham

UT code for WoS chapter

—