Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)