Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Research

Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer

Authors: Mengqin Shen, Xiaoping Zhao, Li Zhao, Liang Shi, Shuxian An, Gang Huang, Jianjun Liu

Published in: Molecular Cancer | Issue 1/2018

Login to get access

Abstract

TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
Appendix
Available only for authorised users
Literature
1.
2.
Wang L, Yu C, Liu Y, Wang J, Li C, Wang Q, Wang P, Wu S, Zhang ZJ. Lung Cancer mortality trends in China from 1988 to 2013: new challenges and opportunities for the government. Int J Environ Res Public Health. 2016;13
3.
4.
Bensaad K, Tsuruta A, Selak MA, Vidal MNC, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006;126:107–20.CrossRefPubMed
5.
Gill JG, Piskounova E, Morrison SJ. Cancer, oxidative stress, and metastasis. Cold Spring Harb Symp Quant Biol. 2016;81:163–75.CrossRefPubMed
6.
Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ, Morrison SJ. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature. 2015;527:186–91.CrossRefPubMedPubMedCentral
7.
White NM, Newsted DW, Masui O, Romaschin AD, Siu KW, Yousef GM. Identification and validation of dysregulated metabolic pathways in metastatic renal cell carcinoma. Tumour Biol. 2014;35:1833–46.CrossRefPubMed
8.
Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, Becker K, Yates JR, Felding-Habermann B. Adaptation of energy metabolism in breast Cancer brain metastases. Cancer Res. 2007;67:1472–86.CrossRefPubMed
9.
Hong M, Xia Y, Zhu Y, Zhao H-H, Zhu H, Xie Y, Fan L, Wang L, Miao K-R, Yu H, et al. TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia. Leuk Res. 2016;50:72–7.CrossRefPubMed
10.
Won KY, Lim SJ, Kim GY, Kim YW, Han SA, Song JY, Lee DK. Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer. Hum Pathol. 2012;43:221–8.CrossRefPubMed
11.
Al-Khayal K, Abdulla M, Al-Obeed O, Kattan WA, Zubaidi A, Vaali-Mohammed M-A, Alsheikh A, Ahmad R. Identification of the TP53-induced glycolysis and apoptosis regulator in various stages of colorectal cancer patients. Oncol Rep. 2016;35:1281–6.CrossRefPubMed
12.
Zhao M, Fan J, Liu Y, Yu Y, Xu J, Wen Q, Zhang J, Fu S, Wang B, Xiang L, et al. Oncogenic role of the TP53-induced glycolysis and apoptosis regulator in nasopharyngeal carcinoma through NF-kappaB pathway modulation. Int J Oncol. 2016;48:756–64.CrossRefPubMed
13.
Wong EY, Wong SC, Chan CM, Lam EK, Ho LY, Lau CP, Au TC, Chan AK, Tsang CM, Tsao SW, et al. TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells. Oncol Lett. 2015;9:569–74.CrossRefPubMed
14.
Zhang H, Gu C, Yu J, Wang Z, Yuan X, Yang L, Wang J, Jia Y, Liu J, Liu F. Radiosensitization of glioma cells by TP53-induced glycolysis and apoptosis regulator knockdown is dependent on thioredoxin-1 nuclear translocation. Free Radic Biol Med. 2014;69:239–48.CrossRefPubMed
15.
Madan E, Gogna R, Kuppusamy P, Bhatt M, Pati U, Mahdi AA. TIGAR induces p53-mediated cell-cycle arrest by regulation of RB–E2F1 complex. Br J Cancer. 2012;107:516–26.CrossRefPubMedPubMedCentral
16.
Peters S, Adjei AA. MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol. 2012;9:314–26.CrossRefPubMed
17.
Ma PC, Jagadeeswaran R, Jagadeesh S, Tretiakova MS, Nallasura V, Fox EA, Hansen M, Schaefer E, Naoki K, Lader A, et al. Functional expression and mutations of c-met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res. 2005;65:1479–88.CrossRefPubMed
18.
Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K, Nakamura T. Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit Rev Oncol Hematol. 2005;53:35–69.CrossRefPubMed
19.
Nakamura Y, Niki T, Goto A, Morikawa T, Miyazawa K, Nakajima J, Fukayama M. C-met activation in lung adenocarcinoma tissues: an immunohistochemical analysis. Cancer Sci. 2007;98:1006–13.CrossRefPubMed
20.
Nakamura Y, Matsubara D, Goto A, Ota S, Sachiko O, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T. Constitutive activation of c-met is correlated with c-met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. Cancer Sci. 2008;99:14–22.CrossRefPubMed
21.
Gumustekin M, Kargi A, Bulut G, Gozukizil A, Ulukus C, Oztop I, Atabey N. HGF/c-met overexpressions, but not met mutation, correlates with progression of non-small cell lung cancer. Pathol Oncol Res. 2012;18:209–18.CrossRefPubMed
22.
Yu H-P, Xie J-M, Li B, Sun Y-H, Gao Q-G, Ding Z-H, Wu H-R, Qin Z-H. TIGAR regulates DNA damage and repair through pentosephosphate pathway and Cdk5-ATM pathway. Sci Rep. 2015;5
23.
Lui VWY, Wong EYL, Ho K, Ng PKS, Lau CPY, Tsui SKW, Tsang CM, Tsao SW, Cheng SH, Ng MHL, et al. Inhibition of c-met downregulates TIGAR expression and reduces NADPH production leading to cell death. Oncogene. 2010;30:1127–34.CrossRefPubMedPubMedCentral
24.
Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta. 2013;1833:3481–98.CrossRefPubMed
25.
Zhao L, Mao Y, Zhao Y, Cao Y, Chen X. Role of multifaceted regulators in cancer glucose metabolism and their clinical significance. Oncotarget. 2016;7:31572–85.PubMedPubMedCentral
26.
Cheung Eric C, Athineos D, Lee P, Ridgway Rachel A, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom Owen J, Vousden Karen H. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell. 2013;25:463–77.CrossRefPubMedPubMedCentral
27.
Lee P, Vousden KH, Cheung EC. TIGAR, TIGAR, burning bright. Cancer Metab. 2014;2(1)
28.
Sinha S, Ghildiyal R, Mehta VS, Sen E. ATM-NFkappaB axis-driven TIGAR regulates sensitivity of glioma cells to radiomimetics in the presence of TNFalpha. Cell Death Dis. 2013;4:e615.CrossRefPubMedPubMedCentral
29.
Chan B, VanderLaan PA, Sukhatme VP. 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-met. Biochem Biophys Res Commun. 2013;439:247–51.CrossRefPubMed
30.
31.
Shay G, Lynch CC, Fingleton B. Moving targets: emerging roles for MMPs in cancer progression and metastasis. Matrix Biol. 2015;44-46:200–6.CrossRefPubMed
Metadata
Title
Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer
Authors
Mengqin Shen
Xiaoping Zhao
Li Zhao
Liang Shi
Shuxian An
Gang Huang
Jianjun Liu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0839-4

Other articles of this Issue 1/2018

Molecular Cancer 1/2018 Go to the issue

Research

Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis

Research

SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex

Review

Role of hypoxia-induced exosomes in tumor biology

Review

Liquid biomarkers in melanoma: detection and discovery

Research

miR-190 suppresses breast cancer metastasis by regulation of TGF-β-induced epithelial–mesenchymal transition

Letter to the Editor

Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits