Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma diation Sensitivity through Attenuated DNA Repair
Univ Calif San Diego, Ludwig Inst Canc Res, San Diego Branch, 9500 Gilman Dr, La Jolla, CA 92093 USA. i, Jie; Cavenee, Webster K.; Kolodner, Richard D.; Chen, Clark C.; Furnari, Frank B..
Show others and affiliations
2019 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 35, no 3, p. 504-518.e7Article in journal (Refereed) Published
Abstract [en]

Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.

Place, publisher, year, edition, pages
Cell Press , 2019. Vol. 35, no 3, p. 504-518.e7
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:kth:diva-248334DOI: 10.1016/j.ccell.2019.01.020ISI: 000461697400015PubMedID: 30827889Scopus ID: 2-s2.0-85062686655OAI: oai:DiVA.org:kth-248334DiVA, id: diva2:1313327
Note

QC 20190503

Available from: 2019-05-03 Created: 2019-05-03 Last updated: 2019-05-03Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Lindahl, Erik

Search in DiVA

By author/editor
Orellana, LauraLindahl, Erik
By organisation
Theoretical & Computational BiophysicsScience for Life Laboratory, SciLifeLab
In the same journal
Cancer Cell
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 34 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf