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TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy.
Cancer Res. 2014 Sep 15; 74(18):5127-38.CR

Abstract

The p53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. In this study, we investigated whether TIGAR might exert dual impacts on cancer cell survival based on its ability to inhibit both apoptosis and autophagy. In liver or lung cancer cells treated with the anticancer drug epirubicin, TIGAR levels increased in a dose- and time-dependent manner. TIGAR silencing enhanced epirubicin-induced elevations in ROS levels and apoptosis rates, in a manner that was blocked by ectopic addition of NADPH or N-acetyl cysteine. These findings were correlated with reduced tumorigenicity and increased chemosensitivity in mouse xenograft tumor assays. In parallel, TIGAR silencing also enhanced the epirubicin-induced activation of autophagy, in a manner that was also blocked by ectopic addition of NADPH. Notably, TIGAR silencing also licensed epirubicin-mediated inactivation of the mTOR pathway, suggesting TIGAR also exerted a negative impact on autophagy. However, genetic or pharmacologic inhibition of autophagy increased epirubicin-induced apoptosis in TIGAR-silenced cells. Overall, our results revealed that TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy. Cancer Res; 74(18); 5127-38. ©2014 AACR.

Authors+Show Affiliations

Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.Department of General Surgery, The First Hospital of Wu Jiang, Suzhou, China.Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.Department of General Surgery, The First Hospital of Wu Jiang, Suzhou, China.Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China. wuhaorong@vip.sina.com qinzhenhong@suda.edu.cn.Department of Pharmacology and Laboratory of Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou, China. wuhaorong@vip.sina.com qinzhenhong@suda.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25085248

Citation

Xie, Jia-Ming, et al. "TIGAR Has a Dual Role in Cancer Cell Survival Through Regulating Apoptosis and Autophagy." Cancer Research, vol. 74, no. 18, 2014, pp. 5127-38.
Xie JM, Li B, Yu HP, et al. TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Res. 2014;74(18):5127-38.
Xie, J. M., Li, B., Yu, H. P., Gao, Q. G., Li, W., Wu, H. R., & Qin, Z. H. (2014). TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. Cancer Research, 74(18), 5127-38. https://doi.org/10.1158/0008-5472.CAN-13-3517
Xie JM, et al. TIGAR Has a Dual Role in Cancer Cell Survival Through Regulating Apoptosis and Autophagy. Cancer Res. 2014 Sep 15;74(18):5127-38. PubMed PMID: 25085248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TIGAR has a dual role in cancer cell survival through regulating apoptosis and autophagy. AU - Xie,Jia-Ming, AU - Li,Bin, AU - Yu,Hong-Pei, AU - Gao,Quan-Geng, AU - Li,Wei, AU - Wu,Hao-Rong, AU - Qin,Zheng-Hong, Y1 - 2014/08/01/ PY - 2014/8/3/entrez PY - 2014/8/3/pubmed PY - 2015/1/21/medline SP - 5127 EP - 38 JF - Cancer research JO - Cancer Res. VL - 74 IS - 18 N2 - The p53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis, resulting in higher intracellular NADPH, lower reactive oxygen species (ROS) and autophagy activity. In this study, we investigated whether TIGAR might exert dual impacts on cancer cell survival based on its ability to inhibit both apoptosis and autophagy. In liver or lung cancer cells treated with the anticancer drug epirubicin, TIGAR levels increased in a dose- and time-dependent manner. TIGAR silencing enhanced epirubicin-induced elevations in ROS levels and apoptosis rates, in a manner that was blocked by ectopic addition of NADPH or N-acetyl cysteine. These findings were correlated with reduced tumorigenicity and increased chemosensitivity in mouse xenograft tumor assays. In parallel, TIGAR silencing also enhanced the epirubicin-induced activation of autophagy, in a manner that was also blocked by ectopic addition of NADPH. Notably, TIGAR silencing also licensed epirubicin-mediated inactivation of the mTOR pathway, suggesting TIGAR also exerted a negative impact on autophagy. However, genetic or pharmacologic inhibition of autophagy increased epirubicin-induced apoptosis in TIGAR-silenced cells. Overall, our results revealed that TIGAR inhibits both apoptosis and autophagy, resulting in a dual impact on tumor cell survival in response to tumor chemotherapy. Cancer Res; 74(18); 5127-38. ©2014 AACR. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/25085248/TIGAR_has_a_dual_role_in_cancer_cell_survival_through_regulating_apoptosis_and_autophagy_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25085248 DB - PRIME DP - Unbound Medicine ER -