ArticleOncotarget2018
The protective autophagy activated by GANT-61 in MYCN amplified neuroblastoma cells is mediated by PERK.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- RCN1 downregulation-driven endoplasmic reticulum stress impairs endothelial function and diabetic foot ulcer healing.Cellular and molecular life sciences : CMLS · 2025Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Wnt/β-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment.Children (Basel, Switzerland) · 2024Review
- Hedgehog signaling regulates the development and treatment of glioblastoma.Oncology letters · 2022Review
- Advances in glioma-associated oncogene (GLI) inhibitors for cancer therapy.Investigational new drugs · 2022Review
- Transcription Factors with Targeting Potential in Gliomas.International journal of molecular sciences · 2022Review
- GANT-61 Induces Autophagy and Apoptosis in Glioblastoma Cells despite their heterogeneity.Cellular and molecular neurobiology · 2021Article
- Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy.Cancers · 2021Article
- Development of hedgehog pathway inhibitors by epigenetically targeting GLI through BET bromodomain for the treatment of medulloblastoma.Acta pharmaceutica Sinica. B · 2021Article
- Inhibition of USP14 induces ER stress-mediated autophagy without apoptosis in lung cancer cell line A549.Cell stress & chaperones · 2020Article
- MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?EMBO molecular medicine · 2020Review
- Targeting autophagy in neuroblastoma.World journal of pediatric surgery · 2020Review
- Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation.Journal of experimental & clinical cancer research : CR · 2019Article
- Hedgehog Signaling Pathway and Autophagy in Cancer.International journal of molecular sciences · 2018Review
- Autophagy Plays a Critical Role in Insulin Resistance- Mediated Chemoresistance in Hepatocellular Carcinoma Cells by Regulating the ER Stress.Journal of Cancer · 2018Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proto-oncogene MYC can trigger the unfolded protein response (UPR). The double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK), one of three primary branches of the UPR, is a key regulator of autophagy, promoting tumorigenesis. Upon activation of PERK, there is an increase in phosphorylation of the eukaryotic initiation factor-2 alpha (eIF2α), which in turn, activates the transcription factor-4 (ATF4), responsible for an increased expression of LC3, a common autophagy marker. PERK is repressed upon GLI1 and GLI2 induction. GANT-61 is an inhibitor of GLI1 and GLI2, known to reduce autophagy in MYCN non-amplified, but not in MYCN amplified neuroblastoma (NB) cells. In our study, we tested the effect of the joint administration of a PERK inhibitor (GSK2606414) and the GLI inhibitor GANT-61 to MYCN amplified and MYCN non-amplified NB cells. Our results suggest that inhibition of PERK impairs GANT-61 induced autophagy in NB cells with MYCN amplification, but had no effect on the MYCN non-amplified NB cells. In summary, PERK seems to be a good therapeutic target for NB. Inhibition of PERK reduces autophagy in MYCN amplified NB cells, thus amplifying the efficacy of the GLI inhibitor GANT-61 in reducing proliferation of this type of cancer cells.
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