Genomes and Genes
Gene Symbol: PRL 3
Description: protein tyrosine phosphatase type IVA, member 3
Alias: PRL-3, PRL-R, PRL3, protein tyrosine phosphatase type IVA 3, phosphatase of regenerating liver 3, potentially prenylated protein tyrosine phosphatase, protein-tyrosine phosphatase 4a3, protein-tyrosine phosphatase of regenerating liver 3
Products: PRL 3
- Zhou J, Wang S, Lu J, Li J, Ding Y. Over-expression of phosphatase of regenerating liver-3 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma. Int J Cancer. 2009;124:1879-86 pubmed publisher..Our results suggest that PRL-3 protein is a valuable marker for progression of NPC patients. High PRL-3 expression is associated with poor overall survival in patients with NPC. ..
- Ustaalioglu B, Bilici A, Barisik N, Aliustaoglu M, Vardar F, Yilmaz B, et al. Clinical importance of phosphatase of regenerating liver-3 expression in breast cancer. Clin Transl Oncol. 2012;14:911-22 pubmed publisher..In addition, triple negative and cerb-B overexpressed tumors, which had worse prognosis compared to hormone receptor positive without cerb-B expressed group, associated with also PRL-3 positivity more than PRL-3 negative group. ..
- Lian S, Meng L, Liu C, Xing X, Song Q, Dong B, et al. PRL-3 activates NF-?B signaling pathway by interacting with RAP1. Biochem Biophys Res Commun. 2013;430:196-201 pubmed publisher..Furthermore, PRL-3 transcriptionally activates RAP1 expression, which is counteracted by ablating p65. Therefore, our results demonstrate PRL-3 as a novel regulator of NF-?B signaling pathway through RAP1. ..
- Peng L, Xing X, Li W, Qu L, Meng L, Lian S, et al. PRL-3 promotes the motility, invasion, and metastasis of LoVo colon cancer cells through PRL-3-integrin beta1-ERK1/2 and-MMP2 signaling. Mol Cancer. 2009;8:110 pubmed publisher..Our results suggest that PRL-3's roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin beta1-ERK1/2-MMP2 signaling. ..
- Xing X, Peng L, Qu L, Ren T, Dong B, Su X, et al. Prognostic value of PRL-3 overexpression in early stages of colonic cancer. Histopathology. 2009;54:309-18 pubmed publisher..0, 95% confidence interval 1.7, 5.3, P < 0.001). PRL-3 may predict poor survival and act as a promising biomarker for individualized therapy for patients with colonic cancer, especially for those diagnosed at an early stage. ..
- Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Watanabe M. Phosphatase of regenerating liver-3 as a prognostic biomarker in histologically node-negative gastric cancer. Oncol Rep. 2009;21:1467-75 pubmed..We propose that PRL-3 expression can have a clinical potential as a prognostic biomarker that may facilitate the development of adjuvant chemotherapy for advanced gastric cancer with stage I disease. ..
- Fagerli U, Holt R, Holien T, Vaatsveen T, Zhan F, Egeberg K, et al. Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells. Blood. 2008;111:806-15 pubmed..In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells. ..
- Kong L, Li Q, Wang L, Liu Z, Sun T. The value and correlation between PRL-3 expression and matrix metalloproteinase activity and expression in human gliomas. Neuropathology. 2007;27:516-21 pubmed..Intermediate MMP2 (MT1-MMP, TIMP-2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas. ..
- Miskad U, Semba S, Kato H, Matsukawa Y, Kodama Y, Mizuuchi E, et al. 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 pubmed..These results suggest that high PRL-3 expression may participate in the progression and metastasis of gastric carcinoma. PRL-3 might be a novel molecular marker for aggressive gastric cancer. ..
- Cai S, Wang Z, Chen C, Wu W, He Y, Zhan W, et al. Role of silencing phosphatase of regenerationg liver-3 expression by microRNA interference in the growth of gastric cancer. Chin Med J (Engl). 2008;121:2534-8 pubmed..001). Knockdown of PRL-3 significantly suppressed the proliferation of SGC7901 cells in vitro and tumor growth in vivo. PRL-3 plays a key role in the growth of gastric cancer. PRL-3 should be considered as a potential therapeutic target. ..
- Kozlov G, Cheng J, Ziomek E, Banville D, Gehring K, Ekiel I. Structural insights into molecular function of the metastasis-associated phosphatase PRL-3. J Biol Chem. 2004;279:11882-9 pubmed..Molecular modeling of the highly homologous PRL-1 and PRL-2 phosphatases revealed unique surface elements that are potentially important for specificity. ..
- Ishii T, Funato Y, Miki H. Thioredoxin-related protein 32 (TRP32) specifically reduces oxidized phosphatase of regenerating liver (PRL). J Biol Chem. 2013;288:7263-70 pubmed publisher..These results suggest that TRP32 maintains the reduced state of PRL and thus regulates the biological function of PRL. ..
- Wang Z, Cai S, He Y, Zhan W, Zhang C, Wu H, et al. Elevated PRL-3 expression was more frequently detected in the large primary gastric cancer and exhibits a poor prognostic impact on the patients. J Cancer Res Clin Oncol. 2009;135:1041-6 pubmed publisher..Its high expression in the primary lesion had a negative impact on the prognosis of the patients. This strongly suggests that PRL-3 should be considered as a prognostic factor. ..
- Park J, Yuen H, Zhou J, Al Aidaroos A, Guo K, Valk P, et al. Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia. EMBO Mol Med. 2013;5:1351-66 pubmed publisher..Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients. ..
- McParland V, Varsano G, Li X, Thornton J, Baby J, Aravind A, et al. The metastasis-promoting phosphatase PRL-3 shows activity toward phosphoinositides. Biochemistry. 2011;50:7579-90 pubmed publisherb>Phosphatase of regenerating liver 3 (PRL-3) is suggested as a biomarker and therapeutic target in several cancers. It has a well-established causative role in cancer metastasis...
- Zeng Q, Si X, Horstmann H, Xu Y, Hong W, Pallen C. Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome. J Biol Chem. 2000;275:21444-52 pubmed
- Bardelli A, Saha S, Sager J, Romans K, Xin B, Markowitz S, et al. PRL-3 expression in metastatic cancers. Clin Cancer Res. 2003;9:5607-15 pubmed..PRL-3 is also expressed in tumor vasculature, regardless of the tumor source. These data raise intriguing questions about the role of protein phosphorylation in angiogenesis and cell-type-specific metastatic processes. ..
- Matter W, Estridge T, Zhang C, Belagaje R, Stancato L, Dixon J, et al. Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling. Biochem Biophys Res Commun. 2001;283:1061-8 pubmed..These data suggest a role for PRL-3 in the modulation of intracellular calcium transients induced by AngII. ..
- Radke I, Gotte M, Kersting C, Mattsson B, Kiesel L, Wülfing 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 pubmed..7 vs 66.7%; P = 0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome. ..
- Wu X, Zeng H, Zhang X, Zhao Y, Sha H, Ge X, et al. Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells. Am J Pathol. 2004;164:2039-54 pubmed..Together, these observations provide convincing evidence that PRL-3 truly plays a causal role in tumor metastasis. ..
- Al Aidaroos A, Yuen H, Guo K, Zhang S, Chung T, Chng W, et al. Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells. J Clin Invest. 2013;123:3459-71 pubmed publisher..We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy. ..
- Tian W, Qu L, Meng L, Liu C, Wu J, Shou C. Phosphatase of regenerating liver-3 directly interacts with integrin ?1 and regulates its phosphorylation at tyrosine 783. BMC Biochem. 2012;13:22 pubmed publisher..Our results revealed a direct interaction between PRL-3 and integrin ?1 and characterized Y783 of integrin ?1 as a bona fide substrate of PRL-3, which is negatively regulated by integrin ?1. ..
- Zhou J, Cheong L, Liu S, Chong P, Mahara S, Bi C, et al. The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia. Mol Cancer. 2012;11:72 pubmed publisher..These data support a role for PRL-3 in BCR-ABL signalling and CML biology and may be a potential therapeutic target downstream of BCR-ABL in TKI resistant mutant cells. ..
- Beekman R, Valkhof M, Erkeland S, Taskesen E, Rockova V, Peeters J, et al. Retroviral integration mutagenesis in mice and comparative analysis in human AML identify reduced PTP4A3 expression as a prognostic indicator. PLoS ONE. 2011;6:e26537 pubmed publisher..In conclusion, our novel strategy has identified PTP4A3 to potentially have a role in AML, on one hand as a candidate HIG contributing to leukemogenesis in mice and on the other hand as a prognostic indicator in human AML. ..
- Jiang Y, Liu X, Rajput A, Geng L, Ongchin M, Zeng Q, et al. Phosphatase PRL-3 is a direct regulatory target of TGFbeta in colon cancer metastasis. Cancer Res. 2011;71:234-44 pubmed publisher..Therefore, a major implication of our findings is that PRL-3 antagonists may offer significant value for antimetastatic therapy in patients with colon cancer. ..
- Laurent C, Valet F, Planque N, Silveri L, Maacha S, Anezo O, et al. High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients. Cancer Res. 2011;71:666-74 pubmed publisher..Protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL3), was identified as a strong predictor of metastasis occurrence...
- Wang J, Kirby C, Herbst R. The tyrosine phosphatase PRL-1 localizes to the endoplasmic reticulum and the mitotic spindle and is required for normal mitosis. J Biol Chem. 2002;277:46659-68 pubmed..Together, these results suggest that PRL-1 function is regulated in a cell cycle-dependent manner and implicate PRL-1 in regulating progression through mitosis, possibly by modulating spindle dynamics. ..
- Liu Y, Li H, Lou X, Lei J. Expression of phosphatase of regenerating liver 1 and 3 mRNA in esophageal squamous cell carcinoma. Arch Pathol Lab Med. 2008;132:1307-12 pubmed publisher..PRL-1 and PRL-3 mRNAs may be involved in and used to predict the metastasis of ESCC. The possibility of using PRL-1 and PRL-3 as the therapeutical target is also discussed. ..
- Xu J, Cao S, Wang L, Xu R, Chen G, Xu Q. VEGF promotes the transcription of the human PRL-3 gene in HUVEC through transcription factor MEF2C. PLoS ONE. 2011;6:e27165 pubmed publisherb>Phosphatase of regenerating liver 3 (PRL-3) is known to be overexpressed in many tumors, and its transcript level is high in the vasculature and endothelial cells of malignant tumor tissue...
- Zhou J, Bi C, Chng W, Cheong L, Liu S, Mahara S, et al. PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy. PLoS ONE. 2011;6:e19798 pubmed publisher..PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation. ..
- Zeng Q, Hong W, Tan Y. Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases homologous to PRL-1. Biochem Biophys Res Commun. 1998;244:421-7 pubmed
- Ma Y, Li B. Expression of phosphatase of regenerating liver-3 in squamous cell carcinoma of the cervix. Med Oncol. 2011;28:775-80 pubmed publisher..PRL-3 may be involved in carcinogenesis of cervix and lymph node metastases of SCC and serves as an unfavorable prognostic factor in patients with SCC. PRL-3 localization in plasma may be related with cancer progress and metastasis. ..
- Molleví D, Aytes A, Padullés L, Martínez Iniesta M, Baixeras N, Salazar R, et al. PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness. Br J Cancer. 2008;99:1718-25 pubmed publisher..Nevertheless, for prognosis purposes, it is imperative to validate the cutoff value of PRL-3 expression in a larger and consecutive series and adjuvant setting. ..
- Hao R, Zhang X, Pan Y, Liu H, Xiang Y, Wan L, et al. Prognostic and metastatic value of phosphatase of regenerating liver-3 in invasive breast cancer. J Cancer Res Clin Oncol. 2010;136:1349-57 pubmed publisher..Increasing the risk of tumor metastasis (OR = 3.889). Our results also imply that PRL-3 might be a novel molecular marker for predicting relapse of invasive breast cancer. ..
- Saha S, Bardelli A, Buckhaults P, Velculescu V, Rago C, St Croix B, et al. A phosphatase associated with metastasis of colorectal cancer. Science. 2001;294:1343-6 pubmed..3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions. ..
- Pathak M, Dhawan D, Lindner D, Borden E, Farver C, Yi T. Pentamidine is an inhibitor of PRL phosphatases with anticancer activity. Mol Cancer Ther. 2002;1:1255-64 pubmed..These observations suggest the potential of pentamidine in anticancer therapies and may provide a basis for developing novel PTPase-targeted therapeutics. ..
- Lai W, Chen S, Wu H, Guan Y, Liu L, Zeng Y, et al. PRL-3 promotes the proliferation of LoVo cells via the upregulation of KCNN4 channels. Oncol Rep. 2011;26:909-17 pubmed publisher..In conclusion, PRL-3 promoted the proliferation of LoVo cells through upregulation of KCNN4 channels which facilitated the G2/M transition. ..
- Choi M, Min S, Jung H, Lee J, Lee T, Lee H, et al. The essential role of FKBP38 in regulating phosphatase of regenerating liver 3 (PRL-3) protein stability. Biochem Biophys Res Commun. 2011;406:305-9 pubmed publisher..Thus, FKBP38 may play a critical role in tumorigenesis. ..
- Min S, Kim D, Heo Y, Kim H, Kim I, Yoo O. Downregulation of p53 by phosphatase of regenerating liver 3 is mediated by MDM2 and PIRH2. Life Sci. 2010;86:66-72 pubmed publisher..These findings demonstrated that PRL-3, like PRL-1, can negatively regulate p53 via the activation of PIRH2 and MDM2 in cancer cells. ..
- Jian M, Nan L, Guocheng J, Qingfu Z, Xueshan Q, Enhua W. Downregulating PRL-3 inhibit migration and invasion of lung cancer cell via RhoA and mDia1. Tumori. 2012;98:370-6 pubmed publisher..The overexpression of phosphatase of regenerating liver-3 (PRL-3) affects the migration and invasion of epithelial cells. Little is known about the substrates or pathways that PRL-3 interacts with...
- Krndija D, Münzberg C, Maass U, Hafner M, Adler G, Kestler H, et al. The phosphatase of regenerating liver 3 (PRL-3) promotes cell migration through Arf-activity-dependent stimulation of integrin ?5 recycling. J Cell Sci. 2012;125:3883-92 pubmed publisherThe formation of metastasis is one of the most critical problems in oncology. The phosphatase of regenerating liver 3 (PRL-3) is a new target in colorectal cancer, mediating metastatic behavior through a promigratory function...
- 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 pubmed publisher..In conclusion, our results indicate that PRL-3 may play an important role for the promotion of CRC cell migration and metastatic potential through direct KRT8 dephosphorylation. ..
- Song R, Qian F, Li Y, Sheng X, Cao S, Xu Q. Phosphatase of regenerating liver-3 localizes to cyto-membrane and is required for B16F1 melanoma cell metastasis in vitro and in vivo. PLoS ONE. 2009;4:e4450 pubmed publisher..These results suggest that cellular localization of PRL-3 is highly correlated with its function in tumor metastasis, and inhibition of PRL-3 prenylation might be a new approach to cancer therapy. ..
- Zheng P, Liu Y, Chen L, Liu X, Xiao Z, Zhao L, et al. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer. J Proteome Res. 2010;9:4897-905 pubmed publisher..The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC. ..
- Polato F, Codegoni A, Fruscio R, Perego P, Mangioni C, Saha S, et al. PRL-3 phosphatase is implicated in ovarian cancer growth. Clin Cancer Res. 2005;11:6835-9 pubmed..This strongly suggests that PRL-3 should be considered as a target for the discovery of new anticancer agents to be tested against this malignancy. ..
- Ming J, Liu N, Gu Y, Qiu X, Wang E. 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 pubmed publisher..PRL-3 up-regulates pERK and Rho expression and activity, facilitating VEGF expression, and accelerating angiogenesis and distant metastasis. How to regulate VEGF-C expression needs to be further studied. ..
- Li J, Guo K, Koh V, Tang J, Gan B, Shi H, et al. Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases. Clin Cancer Res. 2005;11:2195-204 pubmed..The expression of PRL-3 in >10% of primary colorectal cancer samples indicates that PRL-3 may prime the metastatic process. These mAbs will be useful as markers in clinical diagnosis for assessing tumor aggressiveness. ..
- Zhao W, Li Y, Liu X, Zhang L, Wang X. Evaluation of PRL-3 expression, and its correlation with angiogenesis and invasion in hepatocellular carcinoma. Int J Mol Med. 2008;22:187-92 pubmedProtein phosphatase of regenerating liver 3 (PRL-3) is a metastasis-associated phosphatase. Studies have shown that its overexpression increases cell motility and invasiveness...
- Kato H, Semba S, Miskad U, Seo Y, Kasuga M, Yokozaki H. High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: a predictive molecular marker of metachronous liver and lung metastases. Clin Cancer Res. 2004;10:7318-28 pubmed..In addition, PRL-3 is expected to be a promising biomarker for identifying colorectal cancer patients at high risk for distant metastases. ..
- Rios P, Li X, Köhn M. Molecular mechanisms of the PRL phosphatases. FEBS J. 2013;280:505-24 pubmed publisher..Finally, we discuss similarities and differences between the phosphatases of regenerating liver, focusing on their molecular mechanisms and signalling pathways. ..
- Pryczynicz A, Guzinska Ustymowicz K, Chang X, Kiśluk J, Kemona A. PTP4A3 (PRL-3) expression correlate with lymphatic metastases in gastric cancer. Folia Histochem Cytobiol. 2010;48:632-6 pubmed publisher..The protein expression is also significantly associated with gastric carcinomas having a worse prognosis, although patients' survival rate showed lack of correlation with PTP4A3 expression. ..
- Dai N, Lu A, Shou C, Li J. Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer. World J Gastroenterol. 2009;15:1499-505 pubmed..PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection. ..
- Liu Y, Zhou J, Chen J, Gao W, Le Y, Ding Y, et al. PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly. Cancer Biol Ther. 2009;8:1352-9 pubmed..Interestingly, expression of E-cadherin was recovered in SW480 cells after PRL-3 was knocked-down. Our results first linked PRL-3 to cadherin directly. It provided new insights into the regulatory mechanisms of EMT induced by PRL-3. ..
- Matsukawa Y, Semba S, Kato H, Koma Y, Yanagihara K, Yokozaki H. Constitutive suppression of PRL-3 inhibits invasion and proliferation of gastric cancer cell in vitro and in vivo. Pathobiology. 2010;77:155-62 pubmed publisher..Therefore, PRL-3 may be one of the target molecules in gastric cancer therapy. ..
- Kim K, Song J, Jee J, Sheen M, Lee C, Lee T, et al. Structure of human PRL-3, the phosphatase associated with cancer metastasis. FEBS Lett. 2004;565:181-7 pubmed
- Guzinska Ustymowicz K, Pryczynicz A. PRL-3, an emerging marker of carcinogenesis, is strongly associated with poor prognosis. Anticancer Agents Med Chem. 2011;11:99-108 pubmed..PRL-3 overexpression predicts poor prognosis in patients with various carcinomas and is a promising target in the cancer treatment. ..
- Wang Y, Li Z, He J, Li Y, Zhu G, Zhang L, et al. 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 pubmed..Colonic adenocarcinoma cells have the ability to produce PRLs, which may relate to the lymph node metastasis of colonic adenocarcinoma. ..
- Guo K, Li J, Wang H, Osato M, Tang J, Quah S, et al. PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo. Cancer Res. 2006;66:9625-35 pubmed..Our findings provide direct evidence that PRL-3 may be involved in triggering angiogenesis and establishing microvasculature and it may serve as an attractive therapeutic target with respect to both angiogenesis and cancer metastasis. ..