Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

Dong, Zhong; Zhou, Lin; Han, Na; Zhang, Mengxian; Lyu, Xiaojuan

doi:10.1007/s00066-015-0858-7

Cited by 42 publications

(38 citation statements)

References 37 publications

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“…To test this hypothesis, the β-catenin protein expression was determined in the cytoplasm and nucleus of CNE-2 cells, and Western blotting analysis revealed an increase in the nuclear accumulation of β-catenin in the transfection and negative control groups. In a recent study, ionizing radiation was found to induce nuclear translocation and accumulation of β-catenin and enhance the TCF/LEF transcriptional activities in glioblastoma U87 cells, and degrading β-catenin significantly reduced cell invasion [59], which is in agreement with our findings.…”

Section: Discussionsupporting

confidence: 83%

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Kang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Nasopharyngeal carcinoma (NPC) is rare worldwide but remains highly prevalent in endemic regions, notably in southern China. Radiotherapy remains the treatment of choice for NPC, but radioresistance has been identified as a major cause of therapeutic failure. The Wnt/β-catenin signaling has been found to be involved in NPC radioresistance; however, the effect of β-catenin overexpression on radioresistance remains unknown in NPC until now. This study aimed to examine the impact of β-catenin overexpression on the radiosensitivity of human NPC CNE-2 cells. Methods: Immunohistochemistry was performed to detect the β-catenin expression in normal nasopharyngeal specimens and NPC specimens. The human NPC CNE-2 cell line overexpressing β-catenin was modeled by transfection with the pcDNA3.1/Hygro(+)/β-catenin recombinant vector (transfection group), while cells transfected with the pcDNA3.1/Hygro(+) vector served as negative controls and non-transfected cells served as blank controls. The expression of key molecules of the Wnt/β-catenin signaling pathway was determined using Western blotting and qPCR assays, and the changes of radiation sensitivity were measured with a colony-formation assay. Cell viability was measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide) assay. In addition, the cell cycle and apoptosis was detected using flow cytometry and the TCF/LEF transcriptional activity was measured with a Dual Luciferase Reporter Assay System. Results: Immunohistochemical staining showed high β-catenin expression in radioresistant NPC specimens, and low expression in radiosensitive NPC specimens and normal nasopharyngeal specimens. Western blotting and qPCR assays detected higher β-catenin expression in the transfection group than in the negative and blank controls (P < 0.01). Down-regulation of GSK-3β expression (P < 0.05) and up-regulation of Cyclin D1 expression (P < 0.01) was detected in β-catenin overexpressing NPC cells exposed to X-ray radiation relative to negative and blank controls. Colony-formation assay revealed higher D₀, D_q and SF in the transfection group than in the negative and blank control groups post-radiation, and the SER in the transfection group was 0.75-fold and 0.68-fold greater than that in the blank and negative control groups, respectively. MTT assay revealed that the viability of CNE-2 cells was significantly higher in the transfection group (96% ± 8.72%) than in the negative control group (74.67 ± 7.05%) and the blank control group (75.33% ± 7.02%) 24 h post-exposure to 6 Gy X-ray radiation (P < 0.05). X-ray radiation led to a lower proportion of CNE-2 cells at the G2/M phase and a lower apoptotic rate in the transfection group than in the negative and blank control groups (P < 0.05). In addition, the TCF/LEF transcriptional activity was higher in the transfection group than in the negative and blank control groups (P < 0.01), and 6 Gy X-ray radiation elevated the TCF/LEF transcriptional activity relative to 0 Gy radiation ...

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Section: Discussionsupporting

confidence: 83%

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Kang

et al. 2018

Cell Physiol Biochem

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“…Fitting, in our experiment, radio-sensitive SW1463 cells responded with a significant downregulation of ALDH1A3 to radiation. Dong and colleagues demonstrated a role for Wnt/β-catenin signaling in radiation-induced invasion of glioblastoma cells (29). In their model, radiation mediated nuclear accumulation of β-catenin and an up-regulation of Wnt/β-catenin downstream genes.…”

Section: Discussionmentioning

confidence: 99%

“…In their model, radiation mediated nuclear accumulation of β-catenin and an up-regulation of Wnt/β-catenin downstream genes. Pathway inhibition abrogated the pro-invasion effects of radiotherapy (29). Similar to our approach, Ahn et al repeatedly irradiated lung cancer cells to obtain resistant cell populations.…”

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

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Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, non-tumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiological ligand of Frizzled-receptors, which increased resistance to CRT. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to CRT, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy. Implications Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to CRT.

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“…Nuclear β‐catenin has been described as a key protein involved in radioadaptive response, including cell survival when exposed to ionizing radiation . Our immunofluorescence data indicated that β‐catenin redistribution from cell–cell contacts to the cytoplasm and β‐catenin concentration in the nucleus were elevated in cells exposed to RT, and that this nuclear accumulation of β‐catenin was attenuated when DHA was applied in combination with RT.…”

Section: Discussionmentioning

confidence: 58%

Docosahexaenoic acid promotes cell cycle arrest and decreases proliferation through WNT/β‐catenin modulation in colorectal cancer cells exposed to γ‐radiation

et al. 2018

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The effects of radiation are known to be potentiated by N‐3 polyunsaturated fatty acids, which modulate several signaling pathways, but the molecular mechanisms through which these fatty acids enhance the anticancer effects of irradiation in colorectal cancer (CRC) treatment remain poorly elucidated. Here, we aimed to ascertain whether the fatty acid docosahexaenoic acid (DHA) exerts a modulating effect on the response elicited by radiation treatment (RT). Two CRC cell lines, Caco‐2 and HT‐29, were exposed to RT, DHA, or both (DHA + RT) for various times, and then cell viability, proliferation, and clonogenicity were assessed. Moreover, cell cycle, apoptosis, and necrosis were analyzed using flow cytometry, and the involvement of WNT/β‐catenin signaling was investigated by immunofluorescence to determine nuclear β‐catenin, GSK3β phosphorylation status, and TCF/LEF‐activity reporter. DHA and RT applied separately diminished the viability of both HT‐29 and Caco‐2 cells, and DHA + RT caused a further reduction in proliferation mainly in HT‐29 cells, particularly in terms of colony formation. Concomitantly, our results verified cell cycle arrest in G0/G1 phase, a reduction of cyclin D1 expression, and a decrease in GSK3β phosphorylation after the combined treatment. Furthermore, immunofluorescence quantification revealed that nuclear β‐catenin was increased in RT‐exposed cells, but this effect was abrogated in cells exposed to DHA + RT, and the results of TCF/LEF‐activity assays confirmed that DHA attenuated the increase in nuclear β‐catenin activity induced by irradiation. Our finding shows that DHA applied in combination with RT enhanced the antitumor effects of irradiation on CRC cells, and that the underlying mechanism involved the WNT/β‐catenin pathway. © 2018 BioFactors, 45(1):24–34, 2019

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Wnt/β-catenin pathway involvement in ionizing radiation-induced invasion of U87 glioblastoma cells

Abstract: Our data demonstrate a pivotal role of the Wnt/β-catenin pathway in ionizing radiation-induced invasion of glioblastoma cells, and suggest that targeting β-catenin is a promising therapeutic approach to overcoming glioma radioresistance.

Cited by 42 publications

References 37 publications

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Docosahexaenoic acid promotes cell cycle arrest and decreases proliferation through WNT/β‐catenin modulation in colorectal cancer cells exposed to γ‐radiation

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