Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones

Séhédic, Delphine; Cikankowitz, Annabelle; Hindré, François; Davodeau, François; Garcion, Emmanuel

doi:10.1016/j.tips.2015.02.002

Cited by 42 publications

(22 citation statements)

References 202 publications

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“…The postoperative radiotherapy is an established standard treatment for glioma patients [ 26 ]. However, glioblastoma is highly resistant to radiotherapy, which is a common problem with current anticancer therapies [ 27 ]. So having an individualized radiotherapy plan based on each patient’s radio sensibility is necessary for increasing the treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma

Zhang

Huang

et al. 2017

J Exp Clin Cancer Res

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BackgroundMYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has been reported for its role in the genesis and progression of tumors. Forkhead box M1 (FoxM1), another transcriptional factor, is considered to be an independent predictor of poor survival in many solid cancers. The aim of the present study was to investigate the clinical significance of the correlation between MYBL2 and FoxM1 in glioma and the possible mechanism of FoxM1and MYBL2 expression.MethodsMYBL2 and FoxM1expression in cancerous tissues and cell lines were determined by reverse transcription-PCR (RT-PCR), Western blotting and immunostaining. The co-expression of MYBL2 and FoxM1 was analyzed in low-grade glioma (LGG) and glioblastoma (HGG) cohorts of TCGA using cBioportal and UCSC Xena. And, the role of MYBL2 and FoxM1 in glioma cell progression and the underlying mechanisms were studied by using small interfering RNA (si-RNA) and pcDNA3.1 + HAvectors. Furthermore, the effects of MYBL2 and FoxM1 in cell proliferation, cell cycle progression, apoptosis, migration, invasion, and adhesion were determined by cell proliferation assays, flow cytometry analysis, transwell migration and cell adhesion assay.ResultsMYBL2 and FoxM1 expression are significantly associated with clinical stages and overall survival of glioma patients. In cohorts of TCGA, patients with high MYBL2 but without radio-chemotherapy had the highest hazard ratio (adjusted HR = 5.29, 95% CI = 1.475–18.969, P < 0.05). Meanwhile, MYBL2 closely related to the FoxM1 expression in 79 glioma tissues (r = 0.742, p < 0.05) and LGG (r = 0.83) and HGG (r = 0.74) cohorts of TCGA. Down regulation of FoxM1 and MYBL2 by siRNAs induced the cell cycle arrest, apoptosis and EMT of glioma cells. Furthermore, inactivations of Akt/FoxM1 signaling by Akt inhibitor and siRNA-FoxM1 reduce the expression of MYBL2 in glioma cells.ConclusionsMYBL2 is a key downstream factor of Akt/FoxM1 signaling to promote progression of human glioma, and could be a new candidate gene for molecular targeting therapy and biomarker for radiotherapy of glioma.Trial registration CTXY-1300041-3-2. ChiCTR-COC-15006186. Registered date: 13 September 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0573-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma

Zhang

Huang

et al. 2017

J Exp Clin Cancer Res

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“…GBM is the most malignant primary brain tumour in adults. Classified as grade IV by the World Health Organization (WHO), GBM is known as the most frequent, devastating and malignant astrocytic glioma 20 21 . Recently, the main treatment of GBM has included surgical resection, chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway

Liu

Wang

Liu

et al. 2016

Sci Rep

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Ring finger protein 135 (RNF135), located on chromosome 17q11.2, is a RING finger domain-containing E3 ubiquitin ligase that was identified as a bio-marker and therapy target of glioblastoma. In our study, we confirmed that RNF135 was up-regulated in glioblastoma tissues compared with normal brain (NB) tissues, and that RNF135 knockdown inhibited proliferation and migration and led to cell cycle arrest in the G0/G1 phase in vivo. By lowering RNF135 expression, phosphorylated Erk and cell cycle protein CDK4 were down-regulated, while p27Kip1 and p21Waf1/Cip1 were up-regulated in U87 and U251 cells in vitro. In addition, using the immunofluorescence double labelling method, we found that RNF135 and P-Erk were co-localized in the cytoplasm and were highly expressed in glioblastoma samples compared with NB tissues. Moreover, the growth of U87 cell-transplanted tumours in nude mice was inhibited while transduced with Lv-shRNF135. Taken together, our findings demonstrate the biological effects of RNF135 in glioblastoma cell proliferation, migration and cell cycle, and its role in the progression of glioblastoma may be associated with the ERK signal transduction pathway.

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“…In spite of endeavors to exploit new therapeutic strategies for gliomas [4-7], gliomas cunningly develop different compensatory mechanisms [8-11], leading to therapy resistance and unfavorable prognosis. For example, astrocytomas, including glioblastomas (GBMs), can establish microtube-dependent cell interconnection and form functional multicellular network, which protect tumor cells from radiotherapy-induced cell death and develop radioresistance [12].…”

Section: Introductionmentioning

confidence: 99%

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

Xiao

et al. 2017

Cancer Letters

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Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through a caspase 3 dependent mechanism. Evidence in vitro and in vivo indicated that caspase 3 inhibition undermined proangiogenic effects of dying glioma cells. Proteolytic inactivation of caspase 3 in glioma cells reduced tumorigenicity. Importantly, we identified that NF-κB/COX-2/PGE2 axis acted as downstream signaling of caspase 3, mediating proangiogenic response after irradiation. Additionally, VEGF-A, regulated by caspase 3 possibly through phosphorylated eIF4E, was recognized as another downstream factor participating in the proangiogenic response. In conclusion, these data demonstrated that caspase 3 in dying glioma cells supported the proangiogenic response after irradiation by governing NF-κB/COX-2/PGE2 axis and p-eIF4E/VEGF-A signaling. While inducing caspase 3 activation has been a generally-adopted notion in cancer therapeutics, our study counterintuitively illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis, suggesting that radiotherapy combined with caspase 3 inhibitors may be more effective strategies due to restricted post-irradiation angiogenesis.

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Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones

Cited by 42 publications

References 202 publications

Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma

Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma

RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

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