Cristin-resultat-ID: 1250096
Sist endret: 16. august 2019, 13:04
NVI-rapporteringsår: 2015
Resultat
Vitenskapelig artikkel
2015

Divergent androgen regulation of unfolded protein response pathways drives prostate cancer

Bidragsytere:
  • Xia Sheng
  • Yke Jildouw Arnoldussen
  • Margrethe Larsdatter Storm
  • Martina Tesikova
  • Hatice Zeynep Nenseth
  • Sen Zhao
  • mfl.

Tidsskrift

EMBO Molecular Medicine
ISSN 1757-4676
e-ISSN 1757-4684
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2015
Volum: 7
Hefte: 6
Sider: 788 - 801
Open Access

Importkilder

Scopus-ID: 2-s2.0-84930179039

Beskrivelse Beskrivelse

Tittel

Divergent androgen regulation of unfolded protein response pathways drives prostate cancer

Sammendrag

The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion and development of the normal prostate and drive prostate cancer (PCa) growth, they may affect UPR pathways. Here, we show that the canonical UPR pathways are directly and divergently regulated by androgens in PCa cells, through the androgen receptor (AR), which is critical for PCa survival. AR bound to gene regulatory sites and activated the IRE1α branch, but simultaneously inhibited PERK signaling. Inhibition of the IRE1α arm profoundly reduced PCa cell growth in vitro as well as tumor formation in preclinical models of PCa in vivo. Consistently, AR and UPR gene expression were correlated in human PCa, and spliced XBP‐1 expression was significantly upregulated in cancer compared with normal prostate. These data establish a genetic switch orchestrated by AR that divergently regulates the UPR pathways and suggest that targeting IRE1α signaling may have therapeutic utility in PCa.

Bidragsytere

Xia Sheng

  • Tilknyttet:
    Forfatter
    ved Institutt for biovitenskap ved Universitetet i Oslo

Yke Jildouw Arnoldussen

  • Tilknyttet:
    Forfatter
    ved Statens arbeidsmiljøinstitutt
  • Tilknyttet:
    Forfatter
    ved Institutt for biovitenskap ved Universitetet i Oslo

Margrethe Larsdatter Storm

  • Tilknyttet:
    Forfatter
    ved Institutt for biovitenskap ved Universitetet i Oslo

Martina Tesikova

  • Tilknyttet:
    Forfatter
    ved Institutt for biovitenskap ved Universitetet i Oslo

Hatice Zeynep Nenseth

Bidragsyterens navn vises på dette resultatet som Hatice Zeynep Nenseth
  • Tilknyttet:
    Forfatter
    ved Institutt for biovitenskap ved Universitetet i Oslo
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