PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Yeh, Hsin Chih; Li, Ching Chia; Huang, Ching‐Wen; Hour, Tzyh Chyuan; Yeh, Bi-Wen; Li, Wei Ming; Liang, Peir‐In; Chang, Lin; Li, Chien‐Feng; Wu, Wen‐Jeng

doi:10.1016/j.juro.2015.05.101

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…Similar to the cancers described above, upregulated PRL‐3 in tumors has been found in cervix , kidney , glioma , bladder , melanoma , lung , and prostate cancers. As for PRL‐1 and ‐2, using microarray analysis, mRNA levels were shown to be upregulated in pancreatic tumor samples compared with those of normal pancreas .…”

Section: Prl Expression In Tumors and Metastases: Emerging Biomarker supporting

confidence: 70%

“…However, one study indicated that PRL-3 expression has no clinical role in ovarian carcinoma, whereas surprisingly PRL-1 and PRL-2 expression is associated with longer survival [113]. Similar to the cancers described above, upregulated PRL-3 in tumors has been found in cervix [114], kidney [115,116], glioma [117,118], bladder [119], melanoma [120], lung [121], and prostate [122][123][124] cancers. As for PRL-1 and -2, using microarray analysis, mRNA levels were shown to be upregulated in pancreatic tumor samples compared with those of normal pancreas [125].…”

Section: Prl Expression In Tumors and Metastases: Emerging Biomarker mentioning

confidence: 85%

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Physiological and oncogenic roles of the PRL phosphatases

et al. 2018

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The human Phosphatase of Regenerative Liver (PRL) family comprises three members (PRL-1, -2, -3; gene name PTP4A1, PTP4A2, PTP4A3) that are highly expressed in a majority of cancers. This review summarizes our current understanding of PRL biology, including an overview of their evolutionary relationships and the regulatory mechanisms controlling their expression. We provide an updated view on our current knowledge on the PRL functions in solid tumors, hematological cancer, and normal physiology, particularly emphasizing on the use of in vivo mouse models. We also highlight a novel relationship positioning PRL as a central node controlling magnesium homeostasis through an association with the CNNM proteins, which are involved in magnesium transport.

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Section: Prl Expression In Tumors and Metastases: Emerging Biomarker supporting

confidence: 70%

Section: Prl Expression In Tumors and Metastases: Emerging Biomarker mentioning

confidence: 85%

Physiological and oncogenic roles of the PRL phosphatases

et al. 2018

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“…3 They examined the importance of PTP4A3 in paired normal urothelium, noninvasive and invasive UTUC, and nodal metastatic tissue. The PTP4A3 transcript level was assessed in other UTUC samples by real-time reverse transcriptase-polymerase chain reaction.…”

Section: Ptp4a3 Predicts Metastasis and Survival In Upper Tract Cancermentioning

confidence: 99%

This Month in Investigative Urology

Andersson¹

2015

Journal of Urology

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“…While their normal cellular functions are largely unknown, the PRL family has been repeatedly shown to be involved in cancer progression. In particular, PRL-3 is a well-defined biomarker of metastasis in multiple cancer types, including melanoma, colorectal, and ovarian cancers, where PRL-3 expression is significantly higher in metastatic lesions compared to the primary tumor site [6][7][8][9][10][11][12][13][14] . In a comprehensive study of 151 patient samples across eleven common human tumors types, PRL-3 protein expression was upregulated in 80.6% of tumor samples compared to matched normal tissue 15 .…”

Section: Introductionmentioning

confidence: 99%

A screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3)

Rivas

Cerna

Smith

et al. 2020

Preprint

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Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options to target PRL-3 in vivo. Here, we screened 1,443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2.Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad PRL inhibitors, Salirasib and Candesartan blocked PRL-3-induced migration in human embryonic kidney (HEK) cells with no negative impact on cell viability. Both drugs prevented migration of PRL-3 expressing human colorectal cancer cells to a similar degree as the research-grade PRL inhibitor, Thienopyridone, and are selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX5R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.

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PTP4A3 Independently Predicts Metastasis and Survival in Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Abstract: Results imply that PTP4A3 has a role in the carcinogenesis of upper tract urothelial carcinoma. PTP4A3 over expression independently predicted the metastasis and outcome of upper tract urothelial carcinoma, which was even more important in organ confined disease.

Cited by 10 publications

References 29 publications

Physiological and oncogenic roles of the PRL phosphatases

Physiological and oncogenic roles of the PRL phosphatases

This Month in Investigative Urology

A screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3)

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