uu.seUppsala universitets publikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer
Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria..
Vise andre og tillknytning
2017 (engelsk)Inngår i: Genes & Development, ISSN 0890-9369, E-ISSN 1549-5477, Vol. 31, nr 20, s. 2099-2112Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas(G12D) in mouse lung epithelial cells markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas(G12D)-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.

sted, utgiver, år, opplag, sider
2017. Vol. 31, nr 20, s. 2099-2112
Emneord [en]
RANK, energy homeostasis, lung cancer, lung cancer stem-like cells
HSV kategori
Forskningsprogram
Patologi
Identifikatorer
URN: urn:nbn:se:uu:diva-342920DOI: 10.1101/gad.304162.117ISI: 000415923700007PubMedID: 29118048OAI: oai:DiVA.org:uu-342920DiVA, id: diva2:1185705
Tilgjengelig fra: 2018-02-26 Laget: 2018-02-26 Sist oppdatert: 2019-03-29bibliografisk kontrollert

Open Access i DiVA

fulltext(19778 kB)129 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 19778 kBChecksum SHA-512
95627c685c5ff82164905b3c06ead7329b1470da6180039d32c15a9b22b312471aa3240106ad8c57a2ee9db6c9037617d442f710fe9fac6435f3961069fc5ff0
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Botling, JohanMicke, PatrickLa Fleur, Linnea

Søk i DiVA

Av forfatter/redaktør
Botling, JohanMicke, PatrickLa Fleur, Linnea
Av organisasjonen
I samme tidsskrift
Genes & Development

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 129 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 571 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf