Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-12-16

AUTHORS

Oliver D. K. Maddocks, Celia R. Berkers, Susan M. Mason, Liang Zheng, Karen Blyth, Eyal Gottlieb, Karen H. Vousden

ABSTRACT

Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including glycolysis, oxidative phosphorylation, glutaminolysis and anti-oxidant response. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress, a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p53. Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours. More... »

PAGES

542

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature11743

DOI

http://dx.doi.org/10.1038/nature11743

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1024833346

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23242140


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Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature11743'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature11743'


 

This table displays all metadata directly associated to this object as RDF triples.

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