Hedgehog signaling sensitizes Glioma stem cells to endogenous nano-irradiation

Morgenroth, Agnieszka; Vogg, Andreas; Ermert, Katja; Zlatopolskiy, Boris D.; Mottaghy, Felix M.

doi:10.18632/oncotarget.2123

Cited by 32 publications

(36 citation statements)

References 42 publications

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“…Theoretically, expression of every gene in this network may have an influence on the overall functioning of the signaling pathway. Alterations in the expression profiles of many different genes can, therefore, lead to a similar result of a pathway activation or suppression during cancer development [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Signaling pathways activation profiles make better markers of cancer than expression of individual genes

et al. 2014

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Identification of reliable and accurate molecular markers remains one of the major challenges of contemporary biomedicine. We developed a new bioinformatic technique termed OncoFinder that for the first time enables to quantatively measure activation of intracellular signaling pathways basing on transcriptomic data. Signaling pathways regulate all major cellular events in health and disease. Here, we showed that the Pathway Activation Strength (PAS) value itself may serve as the biomarker for cancer, and compared it with the “traditional” molecular markers based on the expression of individual genes. We applied OncoFinder to profile gene expression datasets for the nine human cancer types including bladder cancer, basal cell carcinoma, glioblastoma, hepatocellular carcinoma, lung adenocarcinoma, oral tongue squamous cell carcinoma, primary melanoma, prostate cancer and renal cancer, totally 292 cancer and 128 normal tissue samples taken from the Gene expression omnibus (GEO) repository. We profiled activation of 82 signaling pathways that involve ~2700 gene products. For 9/9 of the cancer types tested, the PAS values showed better area-under-the-curve (AUC) scores compared to the individual genes enclosing each of the pathways. These results evidence that the PAS values can be used as a new type of cancer biomarkers, superior to the traditional gene expression biomarkers.

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Section: Resultsmentioning

confidence: 99%

Signaling pathways activation profiles make better markers of cancer than expression of individual genes

et al. 2014

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“…Indeed, SMO , GLI1 , PTCH1 , CD133 and aldehyde dehydrogenase (ALDH)-expressing GSCs are upregulated post-radiation in GBM neurospheres, which further supports the concept that standard therapies are not able to abolish GSCs [ 115 ]. Additionally, it has been shown that active Hh signaling can sensitize GSCs to endogenous nano-irradiation, through the inhibition of thymidine synthesis [ 117 ].…”

Section: Evidence For the Role Of Hedgehog Signaling In Cancer Stementioning

confidence: 99%

Hedgehog Signaling in the Maintenance of Cancer Stem Cells

Cochrane¹,

Szczepny²,

Watkins³

et al. 2015

Cancers

223

187

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Cancer stem cells (CSCs) represent a rare population of cells with the capacity to self-renew and give rise to heterogeneous cell lineages within a tumour. Whilst the mechanisms underlying the regulation of CSCs are poorly defined, key developmental signaling pathways required for normal stem and progenitor functions have been strongly implicated. Hedgehog (Hh) signaling is an evolutionarily-conserved pathway essential for self-renewal and cell fate determination. Aberrant Hh signaling is associated with the development and progression of various types of cancer and is implicated in multiple aspects of tumourigenesis, including the maintenance of CSCs. Here, we discuss the mounting evidence suggestive of Hh-driven CSCs in the context of haematological malignancies and solid tumours and the novel strategies that hold the potential to block many aspects of the transformation attributed to the CSC phenotype, including chemotherapeutic resistance, relapse and metastasis.

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“…The hedgehog signaling pathway has a vital role in the control of cell differentiation, cell proliferation and embryonic development ( 5 , 7 , 12 ). According to recent studies, aberrant activation of hedgehog signaling is linked to the aggressiveness of multiple tumor types, including GBM ( 21 , 22 ). The results of the present study are therefore consistent with those of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma

Chang

Zhao

Liu

et al. 2015

Molecular Medicine Reports

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Aberrant hedgehog signaling contributes to the development of various malignancies, including glioblastoma (GBM). However, the potential mechanism of hedgehog signaling in GBM migration and invasion has remained to be elucidated. The present study showed that enhanced hedgehog signaling by recombinant human sonic hedgehog N-terminal peptide (rhSHH) promoted the adhesion, invasion and migration of GBM cells, accompanied by increases in mRNA and protein levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. However, inhibition of hedgehog signaling with cyclopamine suppressed the adhesion, invasion and migration of GBM cells, accompanied by decreases in mRNA and protein levels of MMP-2 and -9. Furthermore, it was found that MMP-2- and MMP-9-neutralizing antibodies or GAM6001 reversed the inductive effects of rhSHH on cell migration and invasion. In addition, enhanced hedgehog signaling by rhSHH increased AKT phosphorylation, whereas blockade of hedgehog signaling decreased AKT phosphorylations. Further experiments showed that LY294002, an inhibitor of phosphoinositide-3 kinase (PI3K), decreased rhSHH-induced upregulation of MMP-2 and -9. Finally, the protein expression of glioblastoma-associated oncogene 1 was positively correlated with levels of phosphorylated AKT as well as protein expressions of MMP-2 and -9 in GBM tissue samples. In conclusion, the present study indicated that the hedgehog pathway regulates GBM-cell migration and invasion by increasing MMP-2 and MMP-9 production via the PI3K/AKT pathway.

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Hedgehog signaling sensitizes Glioma stem cells to endogenous nano-irradiation

Cited by 32 publications

References 42 publications

Signaling pathways activation profiles make better markers of cancer than expression of individual genes

Signaling pathways activation profiles make better markers of cancer than expression of individual genes

Hedgehog Signaling in the Maintenance of Cancer Stem Cells

Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma

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