Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-03

AUTHORS

Hans-Guido Wendel, Elisa de Stanchina, Jordan S. Fridman, Abba Malina, Sagarika Ray, Scott Kogan, Carlos Cordon-Cardo, Jerry Pelletier, Scott W. Lowe

ABSTRACT

Evading apoptosis is considered to be a hallmark of cancer, because mutations in apoptotic regulators invariably accompany tumorigenesis. Many chemotherapeutic agents induce apoptosis, and so disruption of apoptosis during tumour evolution can promote drug resistance. For example, Akt is an apoptotic regulator that is activated in many cancers and may promote drug resistance in vitro. Nevertheless, how Akt disables apoptosis and its contribution to clinical drug resistance are unclear. Using a murine lymphoma model, we show that Akt promotes tumorigenesis and drug resistance by disrupting apoptosis, and that disruption of Akt signalling using the mTOR inhibitor rapamycin reverses chemoresistance in lymphomas expressing Akt, but not in those with other apoptotic defects. eIF4E, a translational regulator that acts downstream of Akt and mTOR, recapitulates Akt's action in tumorigenesis and drug resistance, but is unable to confer sensitivity to rapamycin and chemotherapy. These results establish Akt signalling through mTOR and eIF4E as an important mechanism of oncogenesis and drug resistance in vivo, and reveal how targeting apoptotic programmes can restore drug sensitivity in a genotype-dependent manner. More... »

PAGES

332

Journal

TITLE

Nature

ISSUE

6980

VOLUME

428

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature02369

DOI

http://dx.doi.org/10.1038/nature02369

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023725300

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15029198


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nature02369'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nature02369'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nature02369'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nature02369'


 

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