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 Translational Medicine
Published in: Journal of Translational Medicine 1/2016

Open Access 01-12-2016 | Research

Phosphatase of regenerating liver 3 (PRL-3) is overexpressed in human prostate cancer tissue and promotes growth and migration

Authors: Esten N. Vandsemb, Helena Bertilsson, Pegah Abdollahi, Øystein Størkersen, Thea Kristin Våtsveen, Morten Beck Rye, Torstein Baade Rø, Magne Børset, Tobias S. Slørdahl

Published in: Journal of Translational Medicine | Issue 1/2016

Login to get access

Abstract

Background

PRL-3 is a phosphatase implicated in oncogenesis in multiple cancers. In some cancers, notably carcinomas, PRL-3 is also associated with inferior prognosis and increased metastatic potential. In this study we investigated the expression of PRL-3 mRNA in fresh-frozen samples from patients undergoing radical prostatectomy because of prostate cancer (PC) and the biological function of PRL-3 in prostate cancer cells.

Methods

Samples from 41 radical prostatectomy specimens (168 samples in total) divided into low (Gleason score ≤ 6), intermediate (Gleason score = 7) and high (Gleason score ≥ 8) risk were analyzed with gene expression profiling and compared to normal prostate tissue. PRL-3 was identified as a gene with differential expression between healthy and cancerous tissue in these analyses. We used the prostate cancer cell lines PC3 and DU145 and a small molecular inhibitor of PRL-3 to investigate whether PRL-3 had a functional role in cancer. Relative ATP-measurement and thymidine incorporation were used to assess the effect of PRL-3 on growth of the cancer cells. We performed an in vitro scratch assay to investigate the involvement of PRL-3 in migration. Immunohistochemistry was used to identify PRL-3 protein in prostate cancer primary tumor and corresponding lymph node metastases.

Results

Compared to normal prostate tissue, the prostate cancer tissue expressed a significantly higher level of PRL-3. We found PRL-3 to be present in both PC3 and DU145, and that inhibition of PRL-3 led to growth arrest and apoptosis in these two cell lines. Inhibition of PRL-3 led to reduced migration of the PC3 cells. Immunohistochemistry showed PRL-3 expression in both primary tumor and corresponding lymph node metastases.

Conclusions

PRL-3 mRNA was expressed to a greater extent in prostate cancer tissue compared to normal prostate tissue. PRL-3 protein was expressed in both prostate cancer primary tumor and corresponding lymph node metastases. The results from our in vitro assays suggest that PRL-3 promotes growth and migration in prostate cancer. In conclusion, these results imply that PRL-3 has a role in the pathogenesis of prostate cancer.
Appendix
Available only for authorised users
Literature
1.
Saha S, Bardelli A, Buckhaults P, Velculescu VE, Rago C, St Croix B, Romans KE, Choti MA, Lengauer C, Kinzler KW, Vogelstein B. A phosphatase associated with metastasis of colorectal cancer. Science. 2001;294:1343–6.CrossRefPubMed
2.
Peng L, Ning J, Meng L, Shou C. The association of the expression level of protein tyrosine phosphatase PRL-3 protein with liver metastasis and prognosis of patients with colorectal cancer. J Cancer Res Clin Oncol. 2004;130:521–6.CrossRefPubMed
3.
Wang Y, Li ZF, He J, Li YL, Zhu GB, Zhang LH. Expression of the human phosphatases of regenerating liver (PRLs) in colonic adenocarcinoma and its correlation with lymph node metastasis. Int J Colorectal Dis. 2007;22:1179–84.CrossRefPubMed
4.
Mollevi DG, Aytes A, Padulles L, Martinez-Iniesta M, Baixeras N, Salazar R, Ramos E, Figueras J, Capella G, Villanueva A. PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness. Br J Cancer. 2008;99:1718–25.CrossRefPubMedPubMedCentral
5.
Radke I, Gotte M, Kersting C, Mattsson B, Kiesel L, Wulfing P. Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer. Br J Cancer. 2006;95:347–54.CrossRefPubMedPubMedCentral
6.
Ma Y, Li B. Expression of phosphatase of regenerating liver-3 in squamous cell carcinoma of the cervix. Med Oncol. 2011;28:775–80.CrossRefPubMed
7.
Miskad UA, Semba S, Kato H, Matsukawa Y, Kodama Y, Mizuuchi E, Maeda N, Yanagihara K, Yokozaki H. High PRL-3 expression in human gastric cancer is a marker of metastasis and grades of malignancies: an in situ hybridization study. Virchows Arch. 2007;450:303–10.CrossRefPubMed
8.
Li ZR, Wang Z, Zhu BH, He YL, Peng JS, Cai SR, Ma JP, Zhan WH. Association of tyrosine PRL-3 phosphatase protein expression with peritoneal metastasis of gastric carcinoma and prognosis. Surg Today. 2007;37:646–51.CrossRefPubMed
9.
Xing X, Lian S, Hu Y, Li Z, Zhang L, Wen X, Du H, Jia Y, Zheng Z, Meng L, et al. Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma. J Transl Med. 2013;11:309.CrossRefPubMedPubMedCentral
10.
Polato F, Codegoni A, Fruscio R, Perego P, Mangioni C, Saha S, Bardelli A, Broggini M. PRL-3 phosphatase is implicated in ovarian cancer growth. Clin Cancer Res. 2005;11:6835–9.CrossRefPubMed
11.
Ming J, Liu N, Gu Y, Qiu X, Wang EH. PRL-3 facilitates angiogenesis and metastasis by increasing ERK phosphorylation and up-regulating the levels and activities of Rho-A/C in lung cancer. Pathology. 2009;41:118–26.CrossRefPubMed
12.
Beekman R, Valkhof M, Erkeland SJ, Taskesen E, Rockova V, Peeters JK, Valk PJ, Lowenberg B, Touw IP. Retroviral integration mutagenesis in mice and comparative analysis in human AML identify reduced PTP4A3 expression as a prognostic indicator. PLoS One. 2011;6:e26537.CrossRefPubMedPubMedCentral
13.
Zheng P, Meng HM, Gao WZ, Chen L, Liu XH, Xiao ZQ, Liu YX, Sui HM, Zhou J, Liu YH, Li JM. Snail as a key regulator of PRL-3 gene in colorectal cancer. Cancer Biol Ther. 2011;12:742–9.CrossRefPubMed
14.
Wang H, Quah SY, Dong JM, Manser E, Tang JP, Zeng Q. PRL-3 down-regulates PTEN expression and signals through PI3K to promote epithelial-mesenchymal transition. Cancer Res. 2007;67:2922–6.CrossRefPubMed
15.
Pryczynicz A, Guzinska-Ustymowicz K, Niewiarowska K, Cepowicz D, Kemona A. PRL-3 and E-cadherin show mutual interactions and participate in lymph node metastasis formation in gastric cancer. Tumour Biol. 2014;35:6587–92.CrossRefPubMedPubMedCentral
16.
Liu Y, Zhou J, Chen J, Gao W, Le Y, Ding Y, Li J. PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly. Cancer Biol Ther. 2009;8:1352–9.CrossRefPubMed
17.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
18.
Feik E, Schweifer N, Baierl A, Sommergruber W, Haslinger C, Hofer P, Maj-Hes A, Madersbacher S, Gsur A. Integrative analysis of prostate cancer aggressiveness. Prostate. 2013;73:1413–26.CrossRefPubMed
19.
Chen X, Xu S, McClelland M, Rahmatpanah F, Sawyers A, Jia Z, Mercola D. An accurate prostate cancer prognosticator using a seven-gene signature plus Gleason score and taking cell type heterogeneity into account. PLoS One. 2012;7:e45178.CrossRefPubMedPubMedCentral
20.
Bertilsson H, Tessem MB, Flatberg A, Viset T, Gribbestad I, Angelsen A, Halgunset J. Changes in gene transcription underlying the aberrant citrate and choline metabolism in human prostate cancer samples. Clin Cancer Res. 2012;18:3261–9.CrossRefPubMed
21.
Bertilsson H, Angelsen A, Viset T, Skogseth H, Tessem MB, Halgunset J. A new method to provide a fresh frozen prostate slice suitable for gene expression study and MR spectroscopy. Prostate. 2011;71:461–9.CrossRefPubMed
22.
Vatsveen TK, Tian E, Kresse SH, Meza-Zepeda LA, Gabrea A, Glebov O, Dai HY, Sundan A, Kuehl WM, Borset M. OH-2, a hyperdiploid myeloma cell line without an IGH translocation, has a complex translocation juxtaposing MYC near MAFB and the IGK locus. Leuk Res. 2009;33:1670–7.CrossRefPubMed
23.
Xing X, Peng L, Qu L, Ren T, Dong B, Su X, Shou C. Prognostic value of PRL-3 overexpression in early stages of colonic cancer. Histopathology. 2009;54:309–18.CrossRefPubMed
24.
Guo K, Li J, Wang H, Osato M, Tang JP, Quah SY, Gan BQ, Zeng Q. PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo. Cancer Res. 2006;66:9625–35.CrossRefPubMed
25.
Miskad UA, Semba S, Kato H, Yokozaki H. Expression of PRL-3 phosphatase in human gastric carcinomas: close correlation with invasion and metastasis. Pathobiology. 2004;71:176–84.CrossRefPubMed
26.
Zimmerman MW, Homanics GE, Lazo JS. Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer. PLoS One. 2013;8:e58300.CrossRefPubMedPubMedCentral
27.
Liu H, Al-aidaroos AQ, Wang H, Guo K, Li J, Zhang HF, Zeng Q. PRL-3 suppresses c-Fos and integrin alpha2 expression in ovarian cancer cells. BMC Cancer. 2013;13:80.CrossRefPubMedPubMedCentral
28.
Min G, Lee SK, Kim HN, Han YM, Lee RH, Jeong DG, Han DC, Kwon BM. Rhodanine-based PRL-3 inhibitors blocked the migration and invasion of metastatic cancer cells. Bioorg Med Chem Lett. 2013;23:3769–74.CrossRefPubMed
29.
30.
Liang F, Liang J, Wang WQ, Sun JP, Udho E, Zhang ZY. PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation. J Biol Chem. 2007;282:5413–9.CrossRefPubMed
31.
Wu X, Zeng H, Zhang X, Zhao Y, Sha H, Ge X, Zhang M, Gao X, Xu Q. Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol. 2004;164:2039–54.CrossRefPubMedPubMedCentral
32.
Semba S, Mizuuchi E, Yokozaki H. Requirement of phosphatase of regenerating liver-3 for the nucleolar localization of nucleolin during the progression of colorectal carcinoma. Cancer Sci. 2010;101:2254–61.CrossRefPubMed
33.
Basak S, Jacobs SB, Krieg AJ, Pathak N, Zeng Q, Kaldis P, Giaccia AJ, Attardi LD. The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation. Mol Cell. 2008;30:303–14.CrossRefPubMedPubMedCentral
34.
Mizuuchi E, Semba S, Kodama Y, Yokozaki H. Down-modulation of keratin 8 phosphorylation levels by PRL-3 contributes to colorectal carcinoma progression. Int J Cancer. 2009;124:1802–10.CrossRefPubMed
35.
Fagerli UM, Holt RU, Holien T, Vaatsveen TK, Zhan F, Egeberg KW, Barlogie B, Waage A, Aarset H, Dai HY, et al. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells. Blood. 2008;111:806–15.CrossRefPubMedPubMedCentral
36.
Shin Y, Kim GD, Jeon JE, Shin J, Lee SK. Antimetastatic effect of halichondramide, a trisoxazole macrolide from the marine sponge Chondrosia corticata, on human prostate cancer cells via modulation of epithelial-to-mesenchymal transition. Mar Drugs. 2013;11:2472–85.CrossRefPubMedPubMedCentral
37.
Bardelli A, Saha S, Sager JA, Romans KE, Xin B, Markowitz SD, Lengauer C, Velculescu VE, Kinzler KW, Vogelstein B. PRL-3 expression in metastatic cancers. Clin Cancer Res. 2003;9:5607–15.PubMed
38.
Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Waraya M, Kawamata H, Nishimiya H, Nakamura K, Watanabe M. Therapeutic potential of PRL-3 targeting and clinical significance of PRL-3 genomic amplification in gastric cancer. BMC Cancer. 2011;11:122.CrossRefPubMedPubMedCentral
39.
Mollevi DG, Aytes A, Berdiel M, Padulles L, Martinez-Iniesta M, Sanjuan X, Salazar R, Villanueva A. PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts. Mol Cancer. 2009;8:46.CrossRefPubMedPubMedCentral
40.
Jiang Y, Liu XQ, Rajput A, Geng L, Ongchin M, Zeng Q, Taylor GS, Wang J. Phosphatase PRL-3 is a direct regulatory target of TGFbeta in colon cancer metastasis. Cancer Res. 2011;71:234–44.CrossRefPubMedPubMedCentral
Metadata
Title
Phosphatase of regenerating liver 3 (PRL-3) is overexpressed in human prostate cancer tissue and promotes growth and migration
Authors
Esten N. Vandsemb
Helena Bertilsson
Pegah Abdollahi
Øystein Størkersen
Thea Kristin Våtsveen
Morten Beck Rye
Torstein Baade Rø
Magne Børset
Tobias S. Slørdahl
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2016
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-016-0830-z

Other articles of this Issue 1/2016

Journal of Translational Medicine 1/2016 Go to the issue

Research

Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells

Research

Chemotherapy outcome predictive effectiveness by the Oncogramme: pilot trial on stage-IV colorectal cancer

Research

Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes

Research

Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells

Research

Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage

Research

A proof-of-concept study with the tyrosine kinase inhibitor nilotinib in spondyloarthritis
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits