Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
The interplay between AR, EGF receptor and MMP-9 signaling pathways in invasive prostate cancer
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
Visa övriga samt affilieringar
2018 (Engelska)Ingår i: Molecular Medicine, ISSN 1076-1551, E-ISSN 1528-3658, Vol. 24, s. 1-13, artikel-id 34Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Metastatic Prostate cancer (PCa) cells have gained survival and invasive advantages. Epidermal growth factor (EGA) receptor is a receptor tyrosine kinase, which may mediate signalling to promote progression and invasion of various cancers. In this study, we uncovered the molecular mechanisms underlying the interconnection among the androgen receptor (AR), matrix metalloproteinase-9 (MMP9) and EGFR in promoting PCa progression. Methods: Immunohistochemical analysis of the tissue microarrays consisting of primary and metastatic PCa tissues was performed. The clinical importance of EGFR and its association with survivals were analyzed using three cohorts from MSKCC Prostate Oncogenome Project dataset (For primary tumors, n = 181; for metastatic tumors n = 37) and The Cancer Genome Atlas Prostate Adenocarcinoma Provisional dataset (n = 495). Targeted overexpression or inhibition of the proteins of interests was introduced into PCa cell lines. Treatment of PCa cell lines with the compounds was conducted. Immunoblot analysis was performed. Results: We showed that AR, MMP-9 and EGFR are interconnect factors, which may cooperatively promote PCa progression. Altered EGFR expression was associated with poor disease-free survival in PCa patients. Induced overexpression of AR led to an increase in the expression of EGFR, p-GSK-313 and decrease in p27 expression in PCa cell lines in the presence of androgen stimulation. Overexpression of MMP9 significantly induced EGFR expression in PCa cells. Inhibition of PIP5K1a, a lipid kinase that acts upstream of PI3K/AKT greatly reduced expressions of AR, MMP-9 and EGFR. Conclusions: Our findings also suggest that PCa cells may utilize AR, EGFR and MMP-9 pathways in androgen-dependent as well as in castration-resistant conditions. Our data suggest a new therapeutic potential to block cancer metastasis by targeting AR, EGFR and MMP-9 pathways in subsets of PCa patients.

Ort, förlag, år, upplaga, sidor
Springer, 2018. Vol. 24, s. 1-13, artikel-id 34
Nyckelord [en]
Prostate cancer, Cancer metastasis, Epidermal growth factor receptor, Androgen receptor and androgen
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
URN: urn:nbn:se:umu:diva-150769DOI: 10.1186/s10020-018-0035-4ISI: 000437685200001PubMedID: 30134822Scopus ID: 2-s2.0-85053605587OAI: oai:DiVA.org:umu-150769DiVA, id: diva2:1244388
Tillgänglig från: 2018-08-31 Skapad: 2018-08-31 Senast uppdaterad: 2023-03-24Bibliografiskt granskad

Open Access i DiVA

fulltext(4223 kB)303 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 4223 kBChecksumma SHA-512
d32cb5fdd53717b0e871c3e48acef038302b6499c3ab0aec97b06f6731db69eae4357a394f03cf0c152f5165f79a7aca457211efb800f85e9584f4e3c1dc7b55
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Semenas, JuliusPersson, Jenny L.

Sök vidare i DiVA

Av författaren/redaktören
Mandel, AnnaSemenas, JuliusPersson, Jenny L.
Av organisationen
Institutionen för molekylärbiologi (Medicinska fakulteten)
I samma tidskrift
Molecular Medicine
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 303 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 547 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf