Monoacylglycerol Lipase Promotes Progression of Hepatocellular Carcinoma Via NF-κB-mediated Epithelial-mesenchymal Transition

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2016 Nov 26

PMID 27884159

Citations 28

Authors

Weiping Zhu

Yiming Zhao

Jiamin Zhou

Xin Wang

Qi Pan

Ning Zhang

Longrong Wang

Miao Wang

Dihua Zhan

Zeyang Liu

Xigan He

Dening Ma

Shuang Liu

Lu Wang

Affiliations

Soon will be listed here.

Abstract

Background: Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.

Methods: In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.

Results: The expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGL group was markedly poorer than that for the MAGL group in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.

Conclusions: Our findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.

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References

Poon D, Anderson B, Chen L, Tanaka K, Lau W, Van Cutsem E . Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009; 10(11):1111-8. DOI: 10.1016/S1470-2045(09)70241-4. View

Nomura D, Lombardi D, Chang J, Niessen S, Ward A, Long J . Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer. Chem Biol. 2011; 18(7):846-56. PMC: 3149849. DOI: 10.1016/j.chembiol.2011.05.009. View

Forner A, Llovet J, Bruix J . Hepatocellular carcinoma. Lancet. 2012; 379(9822):1245-55. DOI: 10.1016/S0140-6736(11)61347-0. View

Sun H, Jiang L, Luo X, Jin W, He Q, An J . Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer. Oncogene. 2012; 32(2):234-41. PMC: 3901401. DOI: 10.1038/onc.2012.34. View

Yang L, Gao Q, Shi J, Wang Z, Zhang Y, Gao P . Mitogen-activated protein kinase kinase kinase 4 deficiency in intrahepatic cholangiocarcinoma leads to invasive growth and epithelial-mesenchymal transition. Hepatology. 2015; 62(6):1804-16. DOI: 10.1002/hep.28149. View

Nomura D, Long J, Niessen S, Hoover H, Ng S, Cravatt B . Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell. 2010; 140(1):49-61. PMC: 2885975. DOI: 10.1016/j.cell.2009.11.027. View

Zhu X, Zhang J, Zhuang P, Zhu H, Zhang W, Xiong Y . High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008; 26(16):2707-16. DOI: 10.1200/JCO.2007.15.6521. View

Yang J, Weinberg R . Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008; 14(6):818-29. DOI: 10.1016/j.devcel.2008.05.009. View

Polyak K, Weinberg R . Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009; 9(4):265-73. DOI: 10.1038/nrc2620. View

10.

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

11.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

12.

Maacke H, Opitz S, Jost K, Hamdorf W, Henning W, Kruger S . Over-expression of wild-type Rad51 correlates with histological grading of invasive ductal breast cancer. Int J Cancer. 2000; 88(6):907-13. DOI: 10.1002/1097-0215(20001215)88:6<907::aid-ijc11>3.0.co;2-4. View

13.

Muqbil I, Wu J, Aboukameel A, Mohammad R, Azmi A . Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition?. Semin Cancer Biol. 2014; 27:39-45. PMC: 4165636. DOI: 10.1016/j.semcancer.2014.06.003. View

14.

Scheel C, Weinberg R . Phenotypic plasticity and epithelial-mesenchymal transitions in cancer and normal stem cells?. Int J Cancer. 2011; 129(10):2310-4. PMC: 3357895. DOI: 10.1002/ijc.26311. View

15.

Sanchez-Tillo E, Liu Y, de Barrios O, Siles L, Fanlo L, Cuatrecasas M . EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci. 2012; 69(20):3429-56. PMC: 11115078. DOI: 10.1007/s00018-012-1122-2. View

16.

Shaul Y, Freinkman E, Comb W, Cantor J, Tam W, Thiru P . Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition. Cell. 2014; 158(5):1094-1109. PMC: 4250222. DOI: 10.1016/j.cell.2014.07.032. View

17.

Guo F, Parker Kerrigan B, Yang D, Hu L, Shmulevich I, Sood A . Post-transcriptional regulatory network of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions. J Hematol Oncol. 2014; 7:19. PMC: 3973872. DOI: 10.1186/1756-8722-7-19. View

18.

Remmele W, Stegner H . [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe. 1987; 8(3):138-40. View

19.

Zhu W, Zhan D, Wang L, Ma D, Cheng M, Wang H . Proteasome inhibitor MG132 potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells via DR5-dependent pathway. Oncol Rep. 2016; 36(2):845-52. DOI: 10.3892/or.2016.4839. View

20.

Smith A, Roda D, Yap T . Strategies for modern biomarker and drug development in oncology. J Hematol Oncol. 2014; 7:70. PMC: 4189730. DOI: 10.1186/s13045-014-0070-8. View