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Pregled bibliografske jedinice broj: 712869

Functional TLR5 genetic variants affect human colorectal cancer survival


Klimosch, S.N.; Försti, Asta; Eckert, J.; Knežević, Jelena; Bevier, M.; von Schönfels, W.; Heits, N.; Walter, J.; Hinz, S.; Lascorz, J. et al.
Functional TLR5 genetic variants affect human colorectal cancer survival // Cancer research (Baltimore), 73 (2013), 24; 7232-7242 doi:10.1158/0008-5472.CAN-13-1746 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 712869 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Functional TLR5 genetic variants affect human colorectal cancer survival

Autori
Klimosch, S.N. ; Försti, Asta ; Eckert, J. ; Knežević, Jelena ; Bevier, M. ; von Schönfels, W. ; Heits, N. ; Walter, J. ; Hinz, S. ; Lascorz, J. ; Hampe, J. ; Hartl, D. ; Frick, J.S. ; Hemminki, Kari ; Schafmayer, C. ; Weber, Alexander N.

Izvornik
Cancer research (Baltimore) (0008-5472) 73 (2013), 24; 7232-7242

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
TLR5; gene variants; association

Sažetak
Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development.

Izvorni jezik
Engleski



POVEZANOST RADA


Projekti:
098-0000000-2463 - Nedostatak Adenozilhomocistein hidrolaze: Molekularni mehanizmi novog oboljenja (Vugrek, Oliver, MZOS ) ( CroRIS)

Ustanove:
Institut "Ruđer Bošković", Zagreb

Profili:

Avatar Url Jelena Knežević (autor)

Poveznice na cjeloviti tekst rada:

doi cancerres.aacrjournals.org

Citiraj ovu publikaciju:

Klimosch, S.N.; Försti, Asta; Eckert, J.; Knežević, Jelena; Bevier, M.; von Schönfels, W.; Heits, N.; Walter, J.; Hinz, S.; Lascorz, J. et al.
Functional TLR5 genetic variants affect human colorectal cancer survival // Cancer research (Baltimore), 73 (2013), 24; 7232-7242 doi:10.1158/0008-5472.CAN-13-1746 (međunarodna recenzija, članak, znanstveni)
Klimosch, S., Försti, A., Eckert, J., Knežević, J., Bevier, M., von Schönfels, W., Heits, N., Walter, J., Hinz, S. & Lascorz, J. (2013) Functional TLR5 genetic variants affect human colorectal cancer survival. Cancer research (Baltimore), 73 (24), 7232-7242 doi:10.1158/0008-5472.CAN-13-1746.
@article{article, author = {Klimosch, S.N. and F\"{o}rsti, Asta and Eckert, J. and Kne\v{z}evi\'{c}, Jelena and Bevier, M. and von Sch\"{o}nfels, W. and Heits, N. and Walter, J. and Hinz, S. and Lascorz, J. and Hampe, J. and Hartl, D. and Frick, J.S. and Hemminki, Kari and Schafmayer, C. and Weber, Alexander N.}, year = {2013}, pages = {7232-7242}, DOI = {10.1158/0008-5472.CAN-13-1746}, keywords = {TLR5, gene variants, association}, journal = {Cancer research (Baltimore)}, doi = {10.1158/0008-5472.CAN-13-1746}, volume = {73}, number = {24}, issn = {0008-5472}, title = {Functional TLR5 genetic variants affect human colorectal cancer survival}, keyword = {TLR5, gene variants, association} }
@article{article, author = {Klimosch, S.N. and F\"{o}rsti, Asta and Eckert, J. and Kne\v{z}evi\'{c}, Jelena and Bevier, M. and von Sch\"{o}nfels, W. and Heits, N. and Walter, J. and Hinz, S. and Lascorz, J. and Hampe, J. and Hartl, D. and Frick, J.S. and Hemminki, Kari and Schafmayer, C. and Weber, Alexander N.}, year = {2013}, pages = {7232-7242}, DOI = {10.1158/0008-5472.CAN-13-1746}, keywords = {TLR5, gene variants, association}, journal = {Cancer research (Baltimore)}, doi = {10.1158/0008-5472.CAN-13-1746}, volume = {73}, number = {24}, issn = {0008-5472}, title = {Functional TLR5 genetic variants affect human colorectal cancer survival}, keyword = {TLR5, gene variants, association} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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