Liprin-β1 is upregulated in human hepatocellular carcinoma and is associated with advanced tumor stage
Keywords:liprin-β1, hepatocellular carcinoma, cholangiocellular carcinoma, cirrhosis
- Dysregulation of liprin-β1 has been implicated in several types of human cancers. However, the expression of liprin-β1 and its clinicopathologic significance in human hepatocellular carcinoma remains elusive.
- Protein expression of liprin-β1 in hepatocellular carcinoma and cholangiocellular carcinoma was evaluated by immunohistochemistry, and its clinical relevance was assessed. Liprin-β1 was elevated in hepatocellular carcinoma and was related to advanced tumour stage.
- Our findings provide a rationale that liprin-β1 may serve as a potential biomarker for human hepatocellular carcinoma.
Abstract: Liprin-β1 is one of the broadly-expressed liprin family members. Dysregulation of liprin-β1 has been implicated in several types of human cancers. However, the expression of liprin-β1 and its clinicopathological significance in human hepatocellular carcinoma (HCC) remains elusive. We evaluated the protein expression of liprin-β1 in HCC and non-tumor liver tissues by immunohistochemistry, and investigated the relationship between liprin-β1 expression and the clinicopathological attributes of HCC. We found that liprin-β1 expression was significantly higher in HCC than in non-tumor liver tissues. Further analysis showed that higher levels of liprin-β1 in HCC were significantly associated with the advanced clinical stage. Interestingly, liprin-β1 was not detected in cholangiocellular carcinoma specimens. These findings suggest that an elevated expression of liprin-β1 may be involved in HCC progression, providing the rationale that upregulation of liprin-β1 may serve as a novel biomarker for human HCC.
Received: January 16, 2019; Revised: April 3, 2019; Accepted: April 25, 2019; Published online: May 10, 2019
How to cite this article: Li X, Li J, Yang J. Liprin-β1 is up regulated in human hepatocellular carcinoma and is associated with advanced tumor stage. Arch Biol Sci. 2019;71(3):469-74.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global Cancer Statistics. CA Cancer J Clin. 2011;61(2):69-90.
Jemal A, Center MM, DeSantis C, Ward EM. Global Patterns of Cancer Incidence and Mortality Rates and Trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893-907.
Youssef MI, Maghraby H, Youssef EA, El-Sayed MM. Expression of Ki 67 in Hepatocellular Carcinoma Induced by Diethylnitrosamine in Mice and its Correlation with Histopathological Alterations. J Appl Pharm Sci. 2012;2(3):52-9.
Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, Heathcote J, Piratsivuth T, Kew M, Otegbayo JA, Zheng SS, Sarin S, Hamid SS, Modawi SB, Fleig W, Fedail S, Thomson A, Khan A, Malfertheiner P, Lau G, Carillo FJ, Krabshuis J, Le Mair A. Hepatocellular Carcinoma (HCC): a Global Perspective. Arab J Gastroenterol. 2010;11(3):174-9.
Ma S, Lee TK, Zheng BJ, Chan KW, Guan XY. CD133+ HCC Cancer Stem Cells Confer Chemoresistance by Preferential Expression of the Akt/PKB Survival Pathway. Oncogene. 2008;27(12):1749-58.
Stryker E, Johnson KG. LAR, Liprin α and the Regulation of Active Zone Morphogenesis. J Cell Sci. 2007;120(21):3723-8.
Spangler SA, Hoogenraad CC. Liprin-α Proteins: Scaffold Molecules for Synapse Maturation. Biochem Soc Trans. 2007;35(5):1278-82.
Serrapagès C, Medley QG, Tang M, Hart A, Streuli M. Liprins, a Family of LAR Transmembrane Protein-Tyrosine Phosphatase-Interacting Proteins. J Biol Chem. 1998;273(25):15611-20.
Wei Z, Zheng S, Spangler SA, Yu C, Hoogenraad CC, Zhang M. Liprin-Mediated Large Signaling Complex Organization Revealed by the Liprin-α/CASK and Liprin-α/Liprin-β Complex Structures. Mol Cell. 2011;43(4):586-98.
Chiaretti S, Astro V, Chiricozzi E, de Curtis I. Effects of the Scaffold Proteins Liprin-alpha1, beta1 and beta2 on Invasion by Breast Cancer Cells. Biol Cell. 2016;108(3):65-75.
Norrmen C, Vandevelde W, Ny A, Saharinen P, Gentile M, Haraldsen G, Puolakkainen P, Lukanidin E, Dewerchin M, Alitalo K, Petrova TV. Liprin (beta)1 is Highly Expressed in Lymphatic Vasculature and is Important for Lymphatic Vessel Integrity. Blood. 2010;115(4):906-9.
Astro V, Tonoli D, Chiaretti S, Badanai S, Sala K, Zerial M, de Curtis I. Liprin-α1 and ERC1 Control Cell Edge Dynamics by Promoting Focal Adhesion Turnover. Sci Rep. 2016;6:33653.
Luo M, Mengos AE, Mandarino LJ, Sekulic A. Association of Liprin β-1 with Kank Proteins in Melanoma. Exp Dermatol. 2016;25(4):321-3.
Shimada Y, Kohno T, Ueno H, Ino Y, Hayashi H, Nakaoku T, Sakamoto Y, Kondo S, Morizane C, Shimada K, Okusaka T, Hiraoka N. An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma. Oncologist. 2017;22(2):158-64.
Selvanathan SP, Graham GT, Erkizan HV, Dirksen U, Natarajan TG, Dakic A, Yu S, Liu X, Paulsen MT, Ljungman ME, Wu CH, Lawlor ER, Üren A, Toretsky JA. Oncogenic Fusion Protein EWS-FLI1 is a Network Hub that Regulates Alternative Splicing. Proc Natl Acad Sci U S A. 2015;112(11):E1307-16.
Heidenblad M, Jonson T, Mahlamäki EH, Gorunova L, Karhu R, Johansson B, Höglund M. Detailed Genomic Mapping and Expression Analyses of 12p Amplifications in Pancreatic Carcinomas Reveal a 3.5-Mb Target Region for Amplification. Genes Chromosomes Cancer. 2002;34(2):211-23.
Johansson FK, Goransson H, Westermark B. Expression Analysis of Genes Involved in Brain Tumor Progression Driven by Retroviral Insertional Mutagenesis in Mice. Oncogene. 2005;24(24):3896-905.
Plentz RR, Malek NP. Clinical Presentation, Risk Factors and Staging Systems of Cholangiocarcinoma. Best Pract Res Clin Gastroenterol. 2015;29(2):245-52.
Gawrieh S, Baye TM, Carless M, Wallace J, Komorowski R, Kleiner DE, Andris D, Makladi B, Cole R, Charlton M, Curran J, Dyer TD, Charlesworth J, Wilke R, Blangero J, Kissebah AH, Olivier M. Hepatic Gene Networks in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease. Obes Surg. 2010;20(12):1698-709.
Al-Kuraya K, Schraml P, Torhorst J, Tapia C, Zaharieva B, Novotny H, Spichtin H, Maurer R, Mirlacher M, Köchli O, Zuber M, Dieterich H, Mross F, Wilber K, Simon R, Sauter G. Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer. Cancer Res. 2004;64(23):8534-40.
Astro V, Chiaretti S, Magistrati E, Fivaz M, de Curtis I. Liprin-alpha1, ERC1 and LL5 Define Polarized and Dynamic Structures that are Implicated in Cell Migration. J Cell Sci. 2014;127(Pt 17):3862-76.
Tan KD, Zhu Y, Tan HK, Rajasegaran V, Aggarwal A, Wu J, Wu HY, Hwang J, Lim DT, Soo KC, Tan P. Amplification and Overexpression of PPFIA1, a Putative 11q13 Invasion Suppressor Gene, in Head and Neck Squamous Cell Carcinoma. Genes Chromosomes Cancer. 2008;47(4):353-62.
Sala K, Raimondi A, Tonoli D, Tacchetti C, de Curtis I. Identification of a Membrane-less Compartment Regulating Invadosome Function and Motility. Sci Rep. 2018;8(1):1164.
Chiaretti S, de Curtis I. Role of Liprins in the Regulation of Tumor Cell Motility and Invasion. Curr Cancer Drug Targets. 2016;16(3):238-48.
von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W, von Kriegsheim A, Norman JC. ERK2 Drives Tumour Cell Migration in Three-dimensional Microenvironments by Suppressing Expression of Rab17 and Liprin-β2. J Cell Sci. 2012;125(6):1465-77.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T. Proteomic, Functional, and Domain-based Analysis of in vivo 14-3-3 Binding Proteins Involved in Cytoskeletal Regulation and Cellular Organization. Curr Biol. 2004;14(16):1436-50.
Kriajevska M, Fischer-Larsen M, Moertz E, Vorm O, Tulchinsky E, Grigorian M, Ambartsumian N, Lukanidin E. Liprin Beta 1, a Member of the Family of LAR Transmembrane Tyrosine Phosphatase-Interacting Proteins, is a New Target for the Metastasis-associated Protein S100A4 (Mts1). J Biol Chem. 2002;277(7):5229-35.
Tang Y, Liu S, Li N, Guo W, Shi J, Yu H, Zhang L, Wang K, Liu S, Cheng S. 14-3-3zeta Promotes Hepatocellular Carcinoma Venous Metastasis by Modulating Hypoxia-inducible Factor-1alpha. Oncotarget. 2016;7(13):15854-67.
Tang Y, Lv P, Sun Z, Han L, Zhou W. 14-3-3beta Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells by Modulating Expression of MMP2 and MMP9 through PI3K/Akt/NF-kappaB Pathway. PLoS One. 2016;11(1):e0146070.
Zhang J, Zhang DL, Jiao XL, Dong Q. S100A4 Regulates Migration and Invasion in Hepatocellular Carcinoma HepG2 Cells via NF-kappaB-dependent MMP-9 Signal. Eur Rev Med Pharmacol Sci. 2013;17(17):2372-82.
Yan XL, Jia YL, Chen L, Zeng Q, Zhou JN, Fu CJ, Chen HX, Yuan HF, Li ZW, Shi L, Xu YC, Wang JX, Zhang XM, He LJ, Zhai C, Yue W, Pei XT. Hepatocellular Carcinoma-associated Mesenchymal Stem Cells Promote Hepatocarcinoma Progression: Role of the S100A4-miR155-SOCS1-MMP9 Axis. Hepatology. 2013;57(6):2274-86.
van der Vaart B, van Riel WE, Doodhi H, Kevenaar JT, Katrukha EA, Gumy L, Bouchet BP, Grigoriev I, Spangler SA, Yu KL, Wulf PS, Wu J, Lansbergen G, van Battum EY, Pasterkamp RJ, Mimori-Kiyosue Y, Demmers J, Olieric N, Maly IV, Hoogenraad CC, Akhmanova A. CFEOM1-associated Kinesin KIF21A is a Cortical Microtubule Growth Inhibitor. Dev Cell. 2013;27(2):145-60.
Guo Z, Neilson LJ, Zhong H, Murray PS, Zanivan S, Zaidel-Bar R. E-cadherin Interactome Complexity and Robustness Resolved by Quantitative Proteomics. Sci Signal. 2014;7(354):rs7.