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

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2009

Open Access 01-12-2009 | Research

Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells

Authors: Shuhong Zhang, Jianfeng Li, Ying Jiang, Yijun Xu, Chengyong Qin

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2009

Login to get access

Abstract

Background

Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells.

Methods

We examined the expression of PDCD4 in three HCC cell lines with different metastatic potentials, MHCC-97H (high metastatic potential), MHCC-97L (low metastatic potential) and Hep3B (no metastatic potential). A plasmid encoding PDCD4 gene was constructed and then transfected into HCC cells with the lowest PDCD4 expression level. Effects of PDCD4 on cell proliferation, cell apoptosis, gene expression of metastasis tumor antigen 1 (MTA1) and in vitro migration and invasion capacity were assessed after transfection.

Results

Our results showed that the expression level of PDCD4 was inversely correlated to the metastatic potential of HCC cells. After transfection with the PDCD4 gene, HCC cell proliferation rate was significantly decreased, cell apoptosis rate was significantly increased, the expression of MTA1 gene, HCC cell migration and Matrigel invasion were also remarkably inhibited.

Conclusion

PDCD4 expression is inversely correlated to the metastatic potential of HCC cells. PDCD4 can effectively suppress the metastatic potential of HCC cells.
Appendix
Available only for authorised users
Literature
1.
Kirk GD, Bah E, Montesano R: Molecular epidemiology of human liver cancer: insights into etiology, pathogenesis and prevention from The Gambia. West Africa. Carcinogenesis. 2006, 27: 2070-2082. 10.1093/carcin/bgl060.CrossRef
2.
Lai EC, Lau WY: Spontaneous Rupture of Hepatocellular Carcinoma: A Systematic Review. Arch Surg. 2006, 141: 191-198. 10.1001/archsurg.141.2.191.CrossRef
3.
Li X, Pan Y, Fan R, Jin H, Han S, Liu J, Wu K, Fan D: Adenovirus-delivered CIAPIN1 small interfering RNA inhibits HCC growth in vitro and in vivo. Carcinogenesis. 2008, 29: 1587-1593. 10.1093/carcin/bgn052.CrossRef
4.
Clark HP, Carson WF, Kavanagh PV, Ho CP, Shen P, Zagoria RJ: Staging and Current Treatment of Hepatocellular Carcinoma. Radiographics. 2005, 25: S3-23. 10.1148/rg.25si055507.CrossRef
5.
Zhu AX: Systemic Therapy of Advanced Hepatocellular Carcinoma: How Hopeful Should We Be?. Oncologist. 2006, 11: 790-800. 10.1634/theoncologist.11-7-790.CrossRef
6.
Cmarik JL, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H, Matsuhashi S: Colburn NH. Differentially expressed protein PDCD4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci USA. 1999, 96: 14037-14042. 10.1073/pnas.96.24.14037.CrossRef
7.
LaRonde-LeBlanc Nicole, Santhanam Arti, Baker Alyson, Wlodawer Alexander, Colburn Nancy: Structural Basis for Inhibition of Translation by the Tumor Suppressor Pdcd4. Mol Cell Biol. 2007, 27: 147-156. 10.1128/MCB.00867-06.CrossRef
8.
Yang HS, Matthews CP, Clair T, Wang Q, Baker AR, Li CC, Tan TH, Colburn NH: Tumorigenesis Suppressor PDCD4 Down-Regulates Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 Expression To Suppress Colon Carcinoma Cell Invasion. Mol Cell Biol. 2006, 26: 1297-1306. 10.1128/MCB.26.4.1297-1306.2006.CrossRef
9.
Huang C, Jacobson K, Schaller MD: MAP kinases and cell migration. J Cell Sci. 2004, 117: 4619-4628. 10.1242/jcs.01481.CrossRef
10.
Toh Y, Pencil SD, Nicolson GL: A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem. 1994, 269: 22958-22963.
11.
Zhang H, Stephens LC, Kumar R: Metastasis Tumor Antigen Family Proteins during Breast Cancer Progression and Metastasis in a Reliable Mouse Model for Human Breast Cancer. Clin Cancer Res. 2006, 12: 1479-1486. 10.1158/1078-0432.CCR-05-1519.CrossRef
12.
Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, Gschwend JE, Hautmann RE, Sanda MG, Giehl K, Menke A, Chinnaiyan AM, Rubin MA: The Role of Metastasis-Associated Protein 1 in Prostate Cancer Progression. Cancer Res. 2004, 64: 825-829. 10.1158/0008-5472.CAN-03-2755.CrossRef
13.
Kidd M, Nadler B, Mane S, Eick G, Malfertheiner M, Champaneria M, Pfragner R, Modlin I: GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR. Physiol Genomics. 2007, 30: 363-370. 10.1152/physiolgenomics.00251.2006.CrossRef
14.
Lee TK, Man K, Ho JW, Wang XH, Poon RT, Xu Y, Ng KT, Chu AC, Sun CK, Ng IO, Sun HC, Tang ZY, Xu R, Fan ST: FTY720: A Promising Agent for Treatment of Metastatic Hepatocellular Carcinoma. Clin Cancer Res. 2005, 11: 8458-8466. 10.1158/1078-0432.CCR-05-0447.CrossRef
15.
Luo C, Xiao X, Liu D, Chen S, Li M, Xu A, Liu J, Gao S, Wu S, He D: CABYR Is a Novel Cancer-Testis Antigen in Lung Cancer. Clin Cancer Res. 2007, 13: 1288-1297. 10.1158/1078-0432.CCR-06-1742.CrossRef
16.
Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA: Exogenous Expression of N-Cadherin in Breast Cancer Cells Induces Cell Migration, Invasion, and Metastasis. J Cell Biol. 2000, 148: 779-790. 10.1083/jcb.148.4.779.CrossRef
17.
Röcken C, Kientsch-Engel R, Mansfeld S, Stix B, Stubenrauch K, Weigle B, Bühling F, Schwan M, Saeger W: Advanced Glycation End Products and Receptor for Advanced Glycation End Products in AA Amyloidosis. Am J Pathol. 2003, 162: 1213-1220.CrossRef
18.
Mehta R, Kyshtoobayeva A, Kurosaki T, Small EJ, Kim H, Stroup R, McLaren CE, Li KT, Fruehauf JP: Independent Association of Angiogenesis Index with Outcome in Prostate Cancer. Clin Cancer Res. 2001, 7: 81-88.
19.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRef
20.
Das S, Hahn Y, Nagata S, Willingham MC, Bera TK, Lee B, Pastan I: NGEP, a Prostate-Specific Plasma Membrane Protein that Promotes the Association of LNCaP Cells. Cancer Res. 2007, 67: 1594-1601. 10.1158/0008-5472.CAN-06-2673.CrossRef
21.
Li N, Yi F, Sundy CM, Chen L, Hilliker ML, Donley DK, Muldoon DB, Li PL: Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys. Am J Physiol Renal Physiol. 2007, 292: F207-F216. 10.1152/ajprenal.00457.2005.CrossRef
22.
Jaita G, Candolfi M, Zaldivar V, Zárate S, Ferrari L, Pisera D, Castro MG, Seilicovich A: Estrogens Up-Regulate the Fas/FasL Apoptotic Pathway in Lactotropes. Endocrinology. 2005, 146 (11): 4737-44. 10.1210/en.2005-0279.CrossRef
23.
Hu H, Shikama Y, Matsuoka I, Kimura J: Terminally differentiated neutrophils predominantly express Survivin-2 alpha, a dominant-negative isoform of survivin. J Leukoc Biol. 2008, 83 (2): 393-400. 10.1189/jlb.0507282.CrossRef
24.
Liang J, Pan Y, Zhang D, Guo C, Shi Y, Wang J, Chen Y, Wang X, Liu J, Guo X, Chen Z, Qiao T, Fan D: Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS. FASEB J. 2007, 21 (9): 2247-56. 10.1096/fj.06-7799com.CrossRef
25.
Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko SR, Albert DM, Polans AS: Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Invest Ophthalmol Vis Sci. 2006, 47 (9): 3708-16. 10.1167/iovs.06-0119.CrossRef
26.
Cao G, Xiao M, Sun F, Xiao X, Pei W, Li J, Graham SH, Simon RP, Chen J: Cloning of a Novel Apaf-1-Interacting Protein: a Potent Suppressor of Apoptosis and Ischemic Neuronal Cell Death. J Neurosci. 2004, 24: 6189-6201. 10.1523/JNEUROSCI.1426-04.2004.CrossRef
27.
Ishimura N, Isomoto H, Bronk SF, Gores GJ: Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells. Am J Physiol Gastrointest Liver Physiol. 2006, 290: G129-G136. 10.1152/ajpgi.00242.2005.CrossRef
28.
Chen Y, Knösel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S, Ozaki I, Petersen I: Loss of PDCD4 expression in human lung cancer correlates with tumor progression and prognosis. J Pathol. 2003, 200: 640-646. 10.1002/path.1378.CrossRef
29.
Azzoni L, Zatsepina O, Abebe B, Bennett IM, Kanakaraj P, Perussia B: Differential transcriptional regulation of CD161 and a novel gene, 197/15a, by IL-2, IL-15, and IL-12 in NK and T cells. J Immunol. 1998, 161 (7): 3493-500.
30.
Zhang H, Ozaki I, Mizuta T, Hamajima H, Yasutake T, Eguchi Y, Ideguchi H, Yamamoto K, Matsuhashi S: Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Oncogene. 2006, 25 (45): 6101-12. 10.1038/sj.onc.1209634.CrossRef
31.
Göke R, Barth P, Schmidt A, Samans B, Lankat-Buttgereit B: Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21 (Waf1/Cip1). Am J Physiol Cell Physiol. 2004, 287: C1541-C1546. 10.1152/ajpcell.00025.2004.CrossRef
32.
Verschuren EW, Jones N, Evan GI: The cell cycle and how it is steered by Kaposi's sarcoma-associated herpesvirus cyclin. J Gen Virol. 2004, 85 (Pt 6): 1347-61. 10.1099/vir.0.79812-0.CrossRef
33.
Ozpolat B, Akar U, Steiner M, Zorrilla-Calancha I, Tirado-Gomez M, Colburn N, Danilenko M, Kornblau S, Berestein GL: Programmed Cell Death-4 Tumor Suppressor Protein Contributes to Retinoic Acid-Induced Terminal Granulocytic Differentiation of Human Myeloid Leukemia. Mol Cancer Res. 2007, 5: 95-108. 10.1158/1541-7786.MCR-06-0125.CrossRef
34.
Zhang XY, DeSalle LM, Patel JH, Capobianco AJ, Yu D, Thomas-Tikhonenko A, McMahon SB: Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein. Proc Natl Acad Sci USA. 2005, 102: 13968-13973. 10.1073/pnas.0502330102.CrossRef
35.
Stapleton G, Malliri A, Ozanne BW: Downregulated AP-1 activity is associated with inhibition of Protein-Kinase-C-dependent CD44 and ezrin localisation and upregulation of PKC theta in A431 cells. J Cell Sci. 2002, 115: 2713-2724.
Metadata
Title
Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells
Authors
Shuhong Zhang
Jianfeng Li
Ying Jiang
Yijun Xu
Chengyong Qin
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2009
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-28-71

Other articles of this Issue 1/2009

Journal of Experimental & Clinical Cancer Research 1/2009 Go to the issue

Research

The expression of PLK-1 in cervical carcinoma: a possible target for enhancing chemosensitivity

Research

The role of VEGF-C/D and Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma

Review

Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

Research

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

Research

Reduced expression of lamin A/C correlates with poor histological differentiation and prognosis in primary gastric carcinoma

Research

Exogenous incorporation of neugc-rich mucin augments n-glycolyl sialic acid content and promotes malignant phenotype in mouse tumor cell lines
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