Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion

Zhou, Xiuping; Li, Zhi; Shi, Qiong; Jiao, Jiantong; Bian, Wenbin; Xu, Song; Mo, Jianbing; Sang, Ben; Xu, Yinfu; Qian, Jinming; Chao, Yuewen; Yu, Rutong

doi:10.1007/s11060-013-1081-y

Cited by 12 publications

(5 citation statements)

References 40 publications

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“…Therefore, the loss of the p53 gene, which is common in GBM, will lead to HIF-1α stabilization ( Figure 2 B). Other proteins that have been shown to regulate HIF-1α expression under hypoxic conditions leading to increased GBM cell migration and invasion include FAT atypical cadherin 1, integrins αvβ3 and αvβ5, Hypoxia-inducible protein 2 (HIG2), and geranylgeranyltransferase I (GGTI) [ 56 , 57 , 58 , 59 ].…”

Section: Hif Transcription Factorsmentioning

confidence: 99%

The Role of Hypoxia in Glioblastoma Invasion

Monteiro

Hill

Pilkington

et al. 2017

Cells

252

201

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Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patient’s median survival rate ranging from 15 to 17 months. The current treatment for GBM involves tumor resection surgery based on MRI image analysis, followed by radiotherapy and treatment with temozolomide. However, the gradual development of tumor resistance to temozolomide is frequent in GBM patients leading to subsequent tumor regrowth/relapse. For this reason, the development of more effective therapeutic approaches for GBM is of critical importance. Low tumor oxygenation, also known as hypoxia, constitutes a major concern for GBM patients, since it promotes cancer cell spreading (invasion) into the healthy brain tissue in order to evade this adverse microenvironment. Tumor invasion not only constitutes a major obstacle to surgery, radiotherapy, and chemotherapy, but it is also the main cause of death in GBM patients. Understanding how hypoxia triggers the GBM cells to become invasive is paramount to developing novel and more effective therapies against this devastating disease. In this review, we will present a comprehensive examination of the available literature focused on investigating how GBM hypoxia triggers an invasive cancer cell phenotype and the role of these invasive proteins in GBM progression.

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Section: Hif Transcription Factorsmentioning

confidence: 99%

The Role of Hypoxia in Glioblastoma Invasion

Monteiro

Hill

Pilkington

et al. 2017

Cells

252

201

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“…A number of prior reports have documented a role for hypoxia and hypoxia inducible factors (HIFs) 1α and 2α in promoting movement of glioma cells using experimental models (9,13,35,47,62), and begun to elucidate the downstream factors that may mediate this effect (13,20,41,44,59). However, one set of transcription factors known to help drive hypoxia-induced invasion of tumors arising outside the brain-those associated with epithelial to mesenchymal transition (EMT)-has not been extensively studied in the context of GBM motility in hypoxia.…”

Section: Introductionmentioning

confidence: 99%

ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres

et al. 2015

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Diffuse spread through brain parenchyma and the presence of hypoxic foci rimmed by neoplastic cells are two cardinal features of glioblastoma, and low oxygen is thought to drive movement of malignant gliomas in the core of the lesions. Transcription factors associated with epithelial-to-mesenchymal transition (EMT) have been linked to this invasion, and we found that hypoxia increased in vitro invasion up to 4-fold in glioblastoma neurosphere lines and induced the expression of ZEB1. Immunohistochemical assessment of 295 surgical specimens consisting of various types of pediatric and adult brain cancers showed that ZEB1 expression was significantly higher in infiltrative lesions than less invasive tumors such as pilocytic astrocytoma and ependymoma. ZEB1 protein was also present in human fetal periventricular stem and progenitor cells and ZEB1-inhibition impaired migration of in vitro propagated human neural stem cells. The induction of ZEB1 protein in hypoxic glioblastoma neurospheres could be partially blocked by the HIF1alpha inhibitor digoxin. Targeting ZEB1 blocked hypoxiaaugmented invasion of glioblastoma cells in addition to slowing them in normoxia. These data support the role for ZEB1 in invasive and high grade brain tumors and suggest its key role in promoting invasion in the hypoxic tumor core as well as in the periphery.

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“…HIF1α has been shown to play a key role as a transcription factor in hypoxia-induced migration/invasion of several glioblastoma cell lines 9 , 31 – 35 . Since HIF1α nuclear accumulation has been previously reported to be induced by ionizing radiation in tumor cells 36 , we investigated whether HIF1α could be involved in the radiation-induced migration/invasion of GSCs.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have reported that hypoxia may increase the migration/invasion capacity of various glioblastoma cell lines in a HIF1α-dependent manner 31 – 35 , 50 , suggesting that HIF1α is involved in therapeutic failure and GBM relapse 49 . Our study shows that the key factor linking the radiation-induced enhancement of GSCs to stem-like properties is the fact that GSCs are much more prone than differentiated cells to the activation of HIF1α in response to radiation.…”

Section: Discussionmentioning

confidence: 99%

The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation

Gauthier

Saati

Bensalah-Pigeon

et al. 2020

Sci Rep

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Human glioblastoma (GBM) is the most common primary malignant brain tumor. A minor subpopulation of cancer cells, known as glioma stem-like cells (GSCs), are thought to play a major role in tumor relapse due to their stem cell-like properties, their high resistance to conventional treatments and their high invasion capacity. We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). Finally, JMY accumulates in the cytoplasm where it stimulates GSC migration via its actin nucleation-promoting activity. Targeting JMY could thus open the way to the development of new therapeutic strategies to improve the efficacy of radiotherapy and prevent glioma recurrence.

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Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion

Cited by 12 publications

References 40 publications

The Role of Hypoxia in Glioblastoma Invasion

The Role of Hypoxia in Glioblastoma Invasion

ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres

The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation

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