Knockdown of the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Sensitizes Glioma Cells to Hypoxia, Irradiation and Temozolomide

被引：19
|
作者：
Maurer, Gabriele D. [1 ,2 ,3 ,4 ]
Heller, Sonja [1 ,2 ,3 ,4 ]
Wanka, Christina [1 ,2 ,3 ,4 ]
Rieger, Johannes [1 ,2 ,3 ,4 ,5 ]
Steinbach, Joachim P. [1 ,2 ,3 ,4 ]
机构：
[1] Goethe Univ, Univ Hosp Frankfurt, Dr Senckenberg Inst Neurooncol, D-60590 Frankfurt, Germany
[2] Goethe Univ, Univ Hosp Frankfurt, Univ Canc Ctr UCT, D-60590 Frankfurt, Germany
[3] German Canc Res Ctr DKFZ Heidelberg, D-60590 Frankfurt, Germany
[4] German Canc Consortium DKTK, Partner Site Frankfurt Mainz, D-60590 Frankfurt, Germany
[5] Eberhard Karls Univ Tubingen, Univ Hosp Tuebingen, Hertie Inst Clin Brain Res, Interdisciplinary Div Neurooncol, D-72076 Tubingen, Germany
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 05期
关键词：
TP53-induced glycolysis and apoptosis regulator; glioma; hypoxia; irradiation; temozolomide; reactive oxygen species; hypoxia-inducible factor; TUMOR-SUPPRESSOR; P53; GLIOBLASTOMA; RADIOSENSITIZATION; MICROENVIRONMENT; IDENTIFICATION; PROGRESSION; PROGNOSIS; PROTECTS; HIF-1;
D O I：
10.3390/ijms20051061
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been shown to decrease glycolysis, to activate the pentose phosphate pathway, and to provide protection against oxidative damage. Hypoxic regions are considered characteristic of glioblastoma and linked with resistance to current treatment strategies. Here, we established that LNT-229 glioma cell lines stably expressed shRNA constructs targeting TIGAR, and exposed them to hypoxia, irradiation and temozolomide. The disruption of TIGAR enhanced levels of reactive oxygen species and cell death under hypoxic conditions, as well as the effectiveness of irradiation and temozolomide. In addition, TIGAR was upregulated by HIF-1. As a component of a complex network, TIGAR contributes to the metabolic adjustments that arise from either spontaneous or therapy-induced changes in tumor microenvironment.
引用
收藏
页数：14
相关论文
共 47 条
  • [21] The Impact of TP53-Induced Glycolysis and Apoptosis Regulator on Prognosis in Hepatocellular Carcinoma: Association with Tumor Microenvironment and Ferroptosis
    Toshida, Katsuya
    Itoh, Shinji
    Iseda, Norifumi
    Tanaka, Shugo
    Nakazono, Kensuke
    Tomiyama, Takahiro
    Yoshiya, Shohei
    Toshima, Takeo
    Harada, Noboru
    Kohashi, Kenichi
    Taniguchi, Koji
    Oda, Yoshinao
    Yoshizumi, Tomoharu
    LIVER CANCER, 2024,
  • [22] TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia
    Hong, Ming
    Xia, Yi
    Zhu, Yu
    Zhao, Hui-Hui
    Zhu, Han
    Xie, Yue
    Fan, Lei
    Wang, Li
    Miao, Kou-Rong
    Yu, Hui
    Miao, Yu-Qing
    Wu, Wei
    Zhu, Hua-Yuan
    Chen, Yao-Yu
    Xu, Wei
    Qian, Si-Xuan
    Li, Jian-Yong
    LEUKEMIA RESEARCH, 2016, 50 : 72 - 77
  • [23] TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer
    Ko, Ying-Hui
    Domingo-Vidal, Marina
    Roche, Megan
    Lin, Zhao
    Whitaker-Menezes, Diana
    Seifert, Erin
    Capparelli, Claudia
    Tuluc, Madalina
    Birbe, Ruth C.
    Tassone, Patrick
    Curry, Joseph M.
    Navarro-Sabate, Aurea
    Manzano, Anna
    Bartrons, Ramon
    Caro, Jaime
    Martinez-Outschoorn, Ubaldo
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (51) : 26291 - 26303
  • [24] Higher plasma concentration of TP53-induced glycolysis and apoptosis regulator is associated with a lower risk of colorectal cancer metastasis
    Lin, Lin
    Mi, Yanjun
    Li, Xun
    Peng, Cuixin
    Shangguan, Zhaoshui
    Li, Zhibin
    Liu, Suhuan
    CANCER MANAGEMENT AND RESEARCH, 2019, 11 : 263 - 272
  • [25] In silico identification of potential inhibitor for TP53-induced glycolysis and apoptosis regulator in head and neck squamous cell carcinoma
    Vaishali Chandel
    Prem Prakash Sharma
    Seema A. Nayar
    Niraj Kumar Jha
    Saurabh Kumar Jha
    Brijesh Rathi
    Dhruv Kumar
    3 Biotech, 2021, 11
  • [26] In silico identification of potential inhibitor for TP53-induced glycolysis and apoptosis regulator in head and neck squamous cell carcinoma
    Chandel, Vaishali
    Sharma, Prem Prakash
    Nayar, Seema A.
    Jha, Niraj Kumar
    Jha, Saurabh Kumar
    Rathi, Brijesh
    Kumar, Dhruv
    3 BIOTECH, 2021, 11 (03)
  • [27] Glutamine promotes the proliferation of intestinal stem cells via inhibition of TP53-induced glycolysis and apoptosis regulator promoter methylation in burned mice
    Zhang, Panyang
    Wu, Dan
    Zha, Xule
    Su, Sen
    Zhang, Yajuan
    Wei, Yan
    Xia, Lin
    Fan, Shijun
    Peng, Xi
    BURNS & TRAUMA, 2024, 12
  • [28] Oncogenic role of the TP53-induced glycolysis and apoptosis regulator in nasopharyngeal carcinoma through NF-κB pathway modulation
    Zhao, Ming
    Fan, Juan
    Liu, Yong
    Yu, Yanxin
    Xu, Jinhui
    Wen, Qinglian
    Zhang, Jianwen
    Fu, Shaozhi
    Wang, Biqiong
    Xiang, Li
    Feng, Jing
    Wu, Jingbo
    Yang, Linglin
    INTERNATIONAL JOURNAL OF ONCOLOGY, 2016, 48 (02) : 756 - 764
  • [29] Receptor based virtual screening of potential novel inhibitors of tigar [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator
    Poyya, Jagadeesha
    Kumar, D. Jagadeesha
    Nagendra, H. G.
    Dinesh, B.
    Rao, S. J. Aditya
    Joshi, Chandrashekhar G.
    MEDICAL HYPOTHESES, 2021, 156
  • [30] Potent effects of dioscin against hepatocellular carcinoma through regulating TP53-induced glycolysis and apoptosis regulator (TIGAR)-mediated apoptosis, autophagy, and DNA damage (vol 176, pg 919, 2019)
    Mao, Z.
    BRITISH JOURNAL OF PHARMACOLOGY, 2019, 176 (24) : 4788 - 4788
12345