Here we identify atypical protein kinase C ι/λ (aPKC-ι/λ) as a novel GLI regulator in mammals. aPKC-ι/λ and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling.
Gli1 is phosphorylated at S481 by Plk1, and this phosphorylation facilitates the nuclear export and binding of Gli1 with its negative regulator Sufu, leading to a reduction in Hh signaling activity.
The present study explored the possibility of targeting the Hh signal in the treatment of LCNEC by suppressing Hh downstream molecules, Smoothened (Smo) and GLI family zinc finger 1/2 (Gli1/2), in 3 human LCNEC cell lines.
HH signaling keeps XCI in check in pluripotent cells and is transduced by GLI transcription factors to binding sites in Tsix, the antisense repressor of XCI.
This report describes the development of a target-protein-oriented natural-products-isolation (TPO-NAPI) method for Hedgehog inhibitors and the direct GLI1 inhibitor, 5'- O-methyl-3-hydroxyflemingin A (3), which inhibited hedgehog (Hh) signal transduction and diminished characteristics of cancer stem cells.
This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61, the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, and at confirming the chemical nature of its bioactive form.
<b>Background</b>: Accumulating evidence indicates that aberrant activation of the Hedgehog (Hh) signalling pathway by Glioma-associated oncogene (Gli) transcription factors is involved in the aggressive progression of cancers, including ovarian cancer.
The GLI genes, GLI1 and GLI2, are transcription factors that regulate target genes at the distal end of the canonical Hedgehog (HH) signaling pathway (SHH->PTCH->SMO->GLI), tightly regulated in embryonic development, tissue patterning and differentiation.
The hedgehog (HH) signaling pathway is abnormally activated in glioblastoma (GBM); thus, its downstream effector GLI1 may be a suitable target for the treatment of GBM.
Also, ATO suppresses endogenous Hedgehog (Hh) signaling, as it significantly reduces Gli1 transcriptional activity and expression levels of several Hh target genes.
To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients.
The zinc finger transcription factors GLI1 and GLI2 are considered mediators of the HH signal in epidermal cells, although their tumorigenic nature and their relative contribution to tumorigenesis are only poorly understood.
We herein focus on the description of the overlapping activities of two important developmental pathways often exacerbated in cancer, namely Transforming Growth Factor-β (TGF-β) and Hedgehog (HH) signaling, with a special emphasis on the unifying oncogenic role played by GLI1/2 transcription factors.
Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations.
Inhibition of hedgehog (Hh) signalling pathway, including its end effector GLI1, can reverse epithelial-to-mesenchymal transition (EMT) which plays an important role in drug resistance of pancreatic cancer cells to Erlotinib (ETB).
There is now increasing evidence suggesting that 'non-canonical' Hh signalling mechanisms, some of which are independent of GLI-mediated transcription, may be important in cancer and development.
To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in human gastrointestinal stromal tumors (GISTs).
The Hedgehog (Hh) signaling pathway plays critical roles in modulating embryogenesis and maintaining tissue homeostasis, with glioma-associated oncogene (GLI) transcription factors being the main mediators.
The expression of Hh signal-related proteins including Indian hedgehog (Ihh), patched-1 (Ptch1), smoothened (Smo), glioma-associated oncogene homologue1 (Gli1) in cartilage was assessed by immunohistochemistry and Western blot.
Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1.
Blocking the Hh signal using either the Hh pathway inhibitor cyclopamine or Gli1 siRNA led to remarkably decreased cell proliferation in ovarian carcinoma cells.