SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:lup.lub.lu.se:d7d6cb89-ced7-4ee4-a8a0-9b84478f7ab0"
 

Sökning: onr:"swepub:oai:lup.lub.lu.se:d7d6cb89-ced7-4ee4-a8a0-9b84478f7ab0" > A Functional Genomi...

  • Dwane, LisaRoyal College of Surgeons in Ireland (författare)

A Functional Genomic Screen Identifies the Deubiquitinase USP11 as a Novel Transcriptional Regulator of ERα in Breast Cancer

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • 2020

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:d7d6cb89-ced7-4ee4-a8a0-9b84478f7ab0
  • https://lup.lub.lu.se/record/d7d6cb89-ced7-4ee4-a8a0-9b84478f7ab0URI
  • https://doi.org/10.1158/0008-5472.CAN-20-0214DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Approximately 70% of breast cancers express estrogen receptor α (ERα) and depend on this key transcriptional regulator for proliferation and differentiation. While patients with this disease can be treated with targeted antiendocrine agents, drug resistance remains a significant issue, with almost half of patients ultimately relapsing. Elucidating the mechanisms that control ERα function may further our understanding of breast carcinogenesis and reveal new therapeutic opportunities. Here, we investigated the role of deubiquitinases (DUB) in regulating ERα in breast cancer. An RNAi loss-of-function screen in breast cancer cells targeting all DUBs identified USP11 as a regulator of ERα transcriptional activity, which was further validated by assessment of direct transcriptional targets of ERα. USP11 expression was induced by estradiol, an effect that was blocked by tamoxifen and not observed in ERα-negative cells. Mass spectrometry revealed a significant change to the proteome and ubiquitinome in USP11-knockdown (KD) cells in the presence of estradiol. RNA sequencing in LCC1 USP11-KD cells revealed significant suppression of cell-cycle-associated and ERα target genes, phenotypes that were not observed in LCC9 USP11-KD, antiendocrine-resistant cells. In a breast cancer patient cohort coupled with in silico analysis of publicly available cohorts, high expression of USP11 was significantly associated with poor survival in ERα-positive (ERα+) patients. Overall, this study highlights a novel role for USP11 in the regulation of ERα activity, where USP11 may represent a prognostic marker in ERα+ breast cancer. SIGNIFICANCE: A newly identified role for USP11 in ERα transcriptional activity represents a novel mechanism of ERα regulation and a pathway to be exploited for the management of ER-positive breast cancer.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • O'Connor, Aisling EUniversity College Dublin (författare)
  • Das, SudiptoRoyal College of Surgeons in Ireland (författare)
  • Moran, BruceUniversity College Dublin (författare)
  • Mulrane, LaoighseUniversity College Dublin (författare)
  • Pinto-Fernandez, AdanUniversity of Oxford (författare)
  • Ward, ElspethRoyal College of Surgeons in Ireland (författare)
  • Blümel, Anna MRoyal College of Surgeons in Ireland (författare)
  • Cavanagh, Brenton LRoyal College of Surgeons in Ireland (författare)
  • Mooney, BrianRoyal College of Surgeons in Ireland (författare)
  • Dirac, Annette M (författare)
  • Jirström, KarinLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)pat-kji (författare)
  • Kessler, Benedikt M (författare)
  • Ní Chonghaile, Tríona (författare)
  • Bernards, René (författare)
  • Gallagher, William M (författare)
  • O'Connor, Darran P (författare)
  • Royal College of Surgeons in IrelandUniversity College Dublin (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Cancer Research80:22, s. 5076-50881538-7445

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy