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  • Johansson, ErikGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center (author)

Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma

  • Article/chapterEnglish2016

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  • Elsevier BV,2016

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  • LIBRIS-ID:oai:gup.ub.gu.se/240225
  • https://gup.ub.gu.se/publication/240225URI
  • https://doi.org/10.1016/j.yexcr.2016.03.028DOI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • 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.

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  • Zhai, QiweiGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center (author)
  • Zeng, Zhao-junGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center(Swepub:gu)xzenzh (author)
  • Yoshida, TakeshiGothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center (author)
  • Funa, Keiko,1949Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center(Swepub:gu)xfunke (author)
  • Göteborgs universitetSahlgrenska Cancer Center (creator_code:org_t)

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  • In:Experimental Cell Research: Elsevier BV343:2, s. 118-1250014-4827

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Johansson, Erik
Zhai, Qiwei
Zeng, Zhao-jun
Yoshida, Takeshi
Funa, Keiko, 194 ...
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
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Experimental Cel ...
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University of Gothenburg

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