AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells

Shimura, Tsutomu; Noma, Naoto; Sano, Yoh; Ochiai, Yoshihiro; Oikawa, T.; Fukumoto, Manabu; Kunugita, Naoki

doi:10.1016/j.radonc.2014.07.015

Cited by 93 publications

(86 citation statements)

References 30 publications

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“…Shimura et al detected that cells could acquire radioresistance causing by Akt‐mediated enhancing aerobic glycolysis 14. In addition, the poor radio‐response in head neck cancer cells might be also caused by up‐regulation of the Akt pathway 22.…”

Section: Discussionmentioning

confidence: 99%

“…Akt can mediate various steps of glycolysis by post‐transcriptional mechanisms which contain promoting hexokinase activity and up‐regulating expression of glucose transporter Glut1 13. Recent report showed that increased expressions of glucose transporter Glut1 and lactate were examined in acquired radioresistant cells 14. Shimura et al unearthed that inhibition of glycolysis could control required tumour cell radioresistance.…”

Section: Introductionmentioning

confidence: 99%

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Transcription factor ATF3 mediates the radioresistance of breast cancer

Zhao

Sun

et al. 2018

J Cellular Molecular Medi

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This study was designed to research the influence of activating transcription factor 3 (ATF3) on the radioresistance of breast cancer. ATF3 expression was measured by qRT‐PCR and immunohistochemistry. Cancerous cell lines were cultured in vitro, and the expression of ATF3 was gauged by both qRT‐PCR and Western blot before and after the radiation therapy. Cellular cycle and apoptosis were analysed by flow cytometry. Changes in the expression of corresponding proteins in the downstream pathways were identified by Western blot. Tumour xenograft was used to evaluate the effect of ATF3 in vivo. ATF3 was observed stronger in breast cancer tissues and cells. After radiation therapy, the expression of ATF3 in breast cancer cells was up‐regulated. Silencing ATF3 could promote G2/M phase block, facilitate cell apoptosis and decrease clonogenic survival rate. The overexpression of ATF3 could curb G2/M‐phase block, cell apoptosis and increase clonogenic survival rate. Overexpression ATF3 could increase radioresistance by up‐regulating the level of phosphorylation of Akt in the PI3K/Akt signalling pathway. Radioresistance of breast cancer cells could be alleviated by inhibiting the PI3K/Akt signalling pathway. ATF3 could also promote radioresistance in vivo. ATF3 gene was able to promote radioresistance of breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcription factor ATF3 mediates the radioresistance of breast cancer

Zhao

Sun

et al. 2018

J Cellular Molecular Medi

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show abstract

“…As discussed previously, dysregulated or altered energy metabolism is recognized as one of the hallmarks of cancer. Furthermore, it has previously been reported that enhanced aerobic glycolysis of cancer cells contributes to acquired radioresistance (17,18). The present study assessed the rate of glycolysis by measuring glucose consumption and lactate production, which are considered the two major biochemical events of anaerobic glycolysis.…”

Section: Mir-155 Promotes Glycolysis Of Nsclc Cells Via the Upregulatmentioning

confidence: 93%

“…It has previously been reported that radiation induces aerobic glycolysis via reactive oxygen species (17). Furthermore, the oncogene Akt has been shown to promote aerobic glycolysis, which renders cancer cells resistant to irradiation (18), thus indicating that glycolysis may be a target for the development of anticancer therapies. The present study investigated the role of miR-155 in the radiosensitivity of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of microRNA-155 sensitizes lung cancer cells to irradiation via suppression of HK2-modulated glucose metabolism

Zhang

et al. 2016

Molecular Medicine Reports

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Abstract. MicroRNAs (miRNAs) are small non-coding regulatory RNAs, which are involved in the post-transcriptional regulation of gene expression. miRNA (miR)-155, which has previously been reported to be overexpressed in lung cancer, is correlated with poor patient prognosis. The present study aimed to investigate the effects of miR-155 on the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. To explore the roles of miRNAs in the regulation of irradiation sensitivity of human lung cancer cells, the expressions of miR-155 in response to irradiation, have been studied by RT-qPCR, and the putative direct target of miR-155 was identified by western blot and luciferase assays. The results of the present study revealed that the expression of miR-155 was induced by irradiation, thus suggesting a positive correlation between miR-155 and radiosensitivity. Furthermore, overexpression of miR-155 rendered lung cancer cells resistant to irradiation. In addition, hexokinase 2 (HK2) was identified as an indirect target of miR-155; exogenous overexpression of miR-155 upregulated the expression of HK2, whereas inhibition of miR-155 by antisense miRNA suppressed HK2 expression. In addition, HK2-modulated glucose metabolism was significantly upregulated by overexpression of miR-155. Notably, inhibition of miR-155 sensitized lung cancer cells to irradiation via suppression of glucose metabolism. In conclusion, the present study reported a novel function for miR-155 in the regulation of NSCLC cell radiosensitivity, thus suggesting that miR-155 may be considered a therapeutic target for the development of anticancer drugs.

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“…Many of these approaches have mechanistic potential to enhance radiation induced lethal damage within the tumour cell and are presented in table 1 [21][22][23][24][25][26][27][28]. It should be noted that a number of studies examining the combination of novel or targeted agents with radiotherapy in NSCLC are underway [29].…”

Section: Introductionmentioning

confidence: 99%