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01.05.2015 | Original Paper

Suppressed expression of LDHB promotes pancreatic cancer progression via inducing glycolytic phenotype

verfasst von: Jiujie Cui, Ming Quan, Weihua Jiang, Hai Hu, Feng Jiao, Ning Li, Ziliang Jin, Lei Wang, Yu Wang, Liwei Wang

Erschienen in: Medical Oncology | Ausgabe 5/2015

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Abstract

Lactate dehydrogenase B (LDHB) is widely expressed in adult somatic tissue and is one of the two subunits of lactate dehydrogenase, which is the key glycolytic enzyme and catalyzes the interconversion of pyruvate and lactate. However, the roles of LDHB in glycolysis and tumor progression were obscure in different types of cancer. Here, we determined the roles of LDHB in pancreatic cancer development and progression. We found suppressed expression of LDHB in pancreatic cancer which was due to promoter hypermethylation and deceased expression of LDHB led to glycolytic transition. Functional analysis revealed that suppressed expression of LDHB promoted pancreatic cancer cells proliferation, invasion, and migration in hypoxia. Thus, LDHB might function as a suppressor of glycolysis and suppressed pancreatic cancer progression.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.CrossRefPubMed

Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656–70.CrossRefPubMedCentralPubMed

Osthus RC, Shim H, Kim S, Li Q, Reddy R, Mukherjee M, Xu Y, Wonsey D, Lee LA, Dang CV. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J Biol Chem. 2000;275:21797–800.CrossRefPubMed

Dang CV, Semenza GL. Oncogenic alterations of metabolism. Trends Biochem Sci. 1999;24:68–72.CrossRefPubMed

Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M. Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J. 1996;9:1736–42.CrossRefPubMed

Koukourakis MI, Kontomanolis E, Giatromanolaki A, Sivridis E, Liberis V. Serum and tissue LDH levels in patients with breast/gynaecological cancer and benign diseases. Gynecol Obstet Invest. 2009;67:162–8.CrossRefPubMed

Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, Harris AL. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89:877–85.CrossRefPubMedCentralPubMed

Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A, Sivridis E. Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clin Exp Metastas. 2005;22:25–30.CrossRef

Shim H, Dolde C, Lewis BC, Wu CS, Dang G, Jungmann RA, Dalla-Favera R, Dang CV. c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc Natl Acad Sci USA. 1997;94:6658–63.CrossRefPubMedCentralPubMed

10.

Lin Q, Cong X, Yun Z. Differential hypoxic regulation of hypoxia-inducible factors 1alpha and 2alpha. Mol Cancer Res. 2011;9:757–65.CrossRefPubMedCentralPubMed

11.

Leiblich A, Cross SS, Catto JW, Phillips JT, Leung HY, Hamdy FC, Rehman I. Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer. Oncogene. 2006;25:2953–60.CrossRefPubMed

12.

Maekawa M, Taniguchi T, Ishikawa J, Sugimura H, Sugano K, Kanno T. Promoter hypermethylation in cancer silences LDHB, eliminating lactate dehydrogenase isoenzymes 1-4. Clin Chem. 2003;49:1518–20.CrossRefPubMed

13.

Dennison JB, Molina JR, Mitra S, Gonzalez-Angulo AM, Balko JM, Kuba MG, Sanders ME, Pinto JA, Gomez HL, Arteaga CL, et al. Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2013;19:3703–13.CrossRefPubMedCentralPubMed

14.

McCleland ML, Adler AS, Shang Y, Hunsaker T, Truong T, Peterson D, Torres E, Li L, Haley B, Stephan JP, et al. An integrated genomic screen identifies LDHB as an essential gene for triple-negative breast cancer. Cancer Res. 2012;72:5812–23.CrossRefPubMed

15.

Kim JH, Kim EL, Lee YK, Park CB, Kim BW, Wang HJ, Yoon CH, Lee SJ, Yoon G. Decreased lactate dehydrogenase B expression enhances claudin 1-mediated hepatoma cell invasiveness via mitochondrial defects. Exp Cell Res. 2011;317:1108–18.CrossRefPubMed

16.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed

17.

Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–17.CrossRefPubMed

18.

Cui J, Shi M, Xie D, Wei D, Jia Z, Zheng S, Gao Y, Huang S, Xie K. FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression. Clin Cancer Res. 2014;20:2595–606.CrossRefPubMed

19.

Shi M, Cui J, Du J, Wei D, Jia Z, Zhang J, Zhu Z, Gao Y, Xie K. A novel KLF4/LDHA signaling pathway regulates aerobic glycolysis in and progression of pancreatic cancer. Clin Cancer Res. 2014;20:4370–80.CrossRefPubMed

20.

Wang L, Wei D, Huang S, Peng Z, Le X, Wu TT, Yao J, Ajani J, Xie K. Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer. Clin Cancer Res. 2003;9:6371–80.PubMed

21.

Ginjala V, Nacerddine K, Kulkarni A, Oza J, Hill SJ, Yao M, Citterio E, van Lohuizen M, Ganesan S. BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol Cell Biol. 2011;31:1972–82.CrossRefPubMedCentralPubMed

22.

Chen S, Sheng C, Liu D, Yao C, Gao S, Song L, Jiang W, Li J, Huang W. Enhancer of zeste homolog 2 is a negative regulator of mitochondria-mediated innate immune responses. J Immunol. 2013;191:2614–23.CrossRefPubMed

23.

Xue J, Lin X, Chiu WT, Chen YH, Yu G, Liu M, Feng XH, Sawaya R, Medema RH, Hung MC, et al. Sustained activation of SMAD3/SMAD4 by FOXM1 promotes TGF-beta-dependent cancer metastasis. J Clin Invest. 2014;124:564–79.CrossRefPubMedCentralPubMed

24.

Khoo CP, Micklem K, Watt SM. A comparison of methods for quantifying angiogenesis in the Matrigel assay in vitro. Tissue Eng Part C Methods. 2011;17:895–906.CrossRefPubMedCentralPubMed

25.

Draoui N, Feron O. Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. Dis Model Mech. 2011;4:727–32.CrossRefPubMedCentralPubMed

26.

Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439:871–4.CrossRefPubMed

27.

Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet. 2007;39:232–6.CrossRefPubMed

28.

Raaphorst FM. Deregulated expression of Polycomb-group oncogenes in human malignant lymphomas and epithelial tumors. Hum Mol Genet. 2005;14:R93–100.CrossRefPubMed

29.

Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Harris AL. Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small cell lung cancer and tumor-associated stroma. Neoplasia. 2005;7:1–6.CrossRefPubMedCentralPubMed

30.

Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller-Klieser W. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res. 2000;60:916–21.PubMed

Titel: Suppressed expression of LDHB promotes pancreatic cancer progression via inducing glycolytic phenotype
verfasst von: Jiujie Cui
Ming Quan
Weihua Jiang
Hai Hu
Feng Jiao
Ning Li
Ziliang Jin
Lei Wang
Yu Wang
Liwei Wang
Publikationsdatum: 01.05.2015
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 5/2015
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-015-0589-8

Springer Medizin

Suppressed expression of LDHB promotes pancreatic cancer progression via inducing glycolytic phenotype

Abstract

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Springer Medizin

Abstract

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