Prognostic and metastatic value of phosphatase of regenerating liver-3 in invasive breast cancer

Hao, Rutian; Zhang, Xiaohua; Pan, Yun-long; Liu, Haiguang; Xiang, Youqun; Wan, Li; Wu, Ximei

doi:10.1007/s00432-010-0786-y

Cited by 24 publications

(15 citation statements)

References 33 publications

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“…Previous studies have reported PTP4A3 overexpression in several cancers, including breast, gastric and colon cancer (23,24), particularly with metastatic colon and breast cancer. Furthermore, PTP4A3 expression is higher in invasive cancer than normal breast tissue, and protein expression is associated with lymph node positivity (25), as well as reduced disease-free survival (23). …”

Section: Discussionmentioning

confidence: 99%

Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival

et al. 2016

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Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared to estrogen receptor (ER)-positive tumors. Of these, 19 phosphatases were upregulated (0.66-fold; FDR=0.05) in TNBC compared to ER-positive breast cancers. We knocked down 17 overexpressed phosphatases in four triple-negative and four ER-positive breast cancer lines using specific small interfering RNAs and found that depletion of six of these phosphatases significantly reduced growth and anchorage-independent growth of TNBC cells to a greater extent than ER-positive cell lines. Further analysis of the phosphatase PTP4A3 (also known as PRL-3) demonstrated its requirement for G1/S cell cycle progression in all breast cancer cells, but PTP4A3 regulated apoptosis selectively in TNBC cells. In addition, PTP4A3 inhibition reduced the growth of TNBC tumors in vivo. Moreover, in silico analysis revealed the PTP4A3 gene to be amplified in 29% of basal-like breast cancers, and high expression of PTP4A3 could serve as an independent prognostic indicator for worse overall survival. Collectively, these studies define the importance of phosphatase overexpression in TNBC, and lay the foundation for the development of new targeted therapies directed against phosphatases or their respective signaling pathways for TNBC patients.

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Section: Discussionmentioning

confidence: 99%

Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival

et al. 2016

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“…For example, in carcinoma cell lines PTP4A3 expression may lead to down regulation of p53 [18] and it is variably induced by γ-irradiation [19]. Finally, high PTP4A3 expression has been linked to increased tumor aggressiveness in different types of solid tumors, e.g., melanoma, gastric cancer, colon cancer, hepatocellular carcinoma and breast cancer [20], [21], [22], [23], [24], possibly because high PTP4A3 expression leads to increased epithelial-mesenchymal transition [25].…”

Section: Discussionmentioning

confidence: 99%

Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

et al. 2011

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Acute myeloid leukemia (AML) results from multiple genetic and epigenetic aberrations, many of which remain unidentified. Frequent loss of large chromosomal regions marks haplo-insufficiency as one of the major mechanisms contributing to leukemogenesis. However, which haplo-insufficient genes (HIGs) are involved in leukemogenesis is largely unknown and powerful experimental strategies aimed at their identification are currently lacking. Here, we present a new approach to discover HIGs, using retroviral integration mutagenesis in mice in which methylated viral integration sites and neighbouring genes were identified. In total we mapped 6 genes which are flanked by methylated viral integration sites (mVIS). Three of these, i.e., Lrmp, Hcls1 and Prkrir, were up regulated and one, i.e., Ptp4a3, was down regulated in the affected tumor. Next, we investigated the role of PTP4A3 in human AML and we show that PTP4A3 expression is a negative prognostic indicator, independent of other prognostic parameters. 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.

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“…Interestingly, Wang et al found the opposite to be true, where PRL-3 overexpression was associated with reduced the life span of node-negative patients but not node-positive patients (23). Furthermore, a recent study by Hao et al found PRL-3 overexpression in the primary tumor to be significantly correlated with breast cancer metastasis to the lymph node, while Wang et al and Radke et al reported that lymph node metastasis was independent of PRL-3 expression in the primary tumor (12,23,24). Further studies will be required to reconcile these conflicting results.…”

Section: Role Of Prl In Cancermentioning

confidence: 99%

Phosphatase of regenerating liver: a novel target for cancer therapy

Campbell

Zhang

2014

Expert Opinion on Therapeutic Targets

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Importance in the Field Phosphatases of Regenerating Liver (PRLs) are novel oncogenes that interact with many, well-established cell signaling pathways that are misregulated in cancer and is known to drive cancer metastasis when overexpressed. Areas Covered in this Review This review will cover basic information of the discovery and characteristics of the PRL family. We will also report findings on the role of PRL in cancer, cell functions, and cell signaling. Furthermore, PRL’s suitability as a novel drug target will be discussed along with current methods being developed to facilitate PRL inhibition. Expert Opinion PRLs show great potential as novel drug targets for anti-cancer therapeutics. Studies indicate that PRL can perturb major cancer pathways such as Src/ERK1/2 and PTEN/PI3K/Akt. Upregulation of PRLs has also been shown to drive cancer metastasis. However, in order to fully realize its therapeutic potential, a deeper understanding of the function of PRL in normal tissue and in cancer must be obtained. Novel and integrated biochemical, chemical biological and genetic approaches will be needed to identify PRL substrate(s) and to provide proof-of-concept data on the druggability of the PRL phosphatases.

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Prognostic and metastatic value of phosphatase of regenerating liver-3 in invasive breast cancer

Abstract: These results strongly suggest that PRL-3 expression can indicate the potential role of LNM to some extent. 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.

Cited by 24 publications

References 33 publications

Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival

Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival

Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

Phosphatase of regenerating liver: a novel target for cancer therapy

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