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Göteborgs universitets publikationer

Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma

Författare och institution:
Erik Johansson (Sahlgrenska Cancer Center); Qiwei Zhai (Sahlgrenska Cancer Center); Zhao-jun Zeng (Sahlgrenska Cancer Center); Takeshi Yoshida (Sahlgrenska Cancer Center); Keiko Funa (Sahlgrenska Cancer Center)
Publicerad i:
Experimental Cell Research, 343 ( 2 ) s. 118-125
ISSN:
0014-4827
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
TLX (also called NR2E1) is an orphan nuclear receptor that maintains sternness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-beta (TGF-beta) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-beta has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-beta signaling we wanted to find out if there is any interaction between TLX and TGF-beta in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-beta signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-beta receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-beta receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-beta target genes. The interaction between TLX and TGF-beta may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin
Nyckelord:
TLX, TGF-beta, TGF-beta receptor II, Smurf1, glioblastoma, growth-factor-beta, ubiquitin-mediated degradation, cell-cycle arrest, i, receptor, tailless, smad7, gene, smurf1, Oncology, Cell Biology
Postens nummer:
240225
Posten skapad:
2016-08-15 10:52

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