PRL-3

Protein phosphatases are primarily responsible for dephosphorylation modification within signal transduction pathways. Phosphatase of regenerating liver-3 (PRL-3) is a dual-specific phosphatase implicated in cancer pathogenesis. Understanding PRL-3's intricate functions and developing targeted therapies is crucial for advancing cancer treatment. This review highlights its regulatory mechanisms, expression patterns, and multifaceted roles in cancer progression. PRL-3's involvement in proliferation, migration, invasion, metastasis, angiogenesis, and drug resistance is discussed...

Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands...

Background: Colon cancer is the one of leading causes of cancer-related death. Chemotherapy, radiotherapy and immunotherapy will be the mainstream in inoperable advanced cancer in clinics. Precision treatment is still lack in colon cancer. Materials and Methods: We developed a series of mAbs targeting PRL-3 through different types of immunogens. The binding domains of mAbs were identified through the ELISA and Western blotting experiments. The antitumor activity of mAbs was verified by cell proliferation, migration and invasion experiments...

Phosphatase of regenerating liver 3 (PRL-3) is associated with cancer metastasis and has been shown to interact with the cyclin and CBS domain divalent metal cation transport mediator (CNNM) family of proteins to regulate the intracellular concentration of magnesium and other divalent metals. Despite PRL-3's importance in cancer, factors that regulate PRL-3's phosphatase activity and its interactions with CNNM proteins remain unknown. Here, we show that divalent metal ions, including magnesium, calcium, and manganese, have no impact on PRL-3's structure, stability, phosphatase activity, or CNNM binding capacity, indicating that PRL-3 does not act as a metal sensor, despite its interaction with CNNM metal transporters...

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3's oncogenic functions are not well understood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3 with a KD of 30-300 nM and no activity towards highly homologous family members PRL-1 and PRL-2. We found that longer and charged N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide new insights into PRL-3 trafficking and function...

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of mortality worldwide. Phosphatase regenerating liver 3 (PRL-3) was associated with cancer metastasis. However, the significance of PRL-3 in the prognosis of HCC remains elusive. The aim of this study was to elucidate the role of PRL-3 in HCC metastasis and its prognosis. METHODS: The expressions of PRL-3 in cancer tissues isolated from 114 HCC patients, who underwent curative hepatectomy from May to November in 2008, were analyzed by immunohistochemistry, and its prognostic significance was evaluated...

BACKGROUND: Phosphatase of regenerating liver-3 (PRL-3) is involved in cellular processes driving metastasis, cell proliferation, invasion, motility and survival. It has been shown to be upregulated and overexpressed in cancer tissue, in contrast to low or no expression in most normal tissue. PRL3-zumab is a first-in-class humanized antibody that specifically binds to PRL-3 oncotarget with high affinity and has been shown to reduce tumor growth and increase survival. OBJECTIVE: In the study, we aimed to determine the safety and efficacy of PRL3-zumab in patients with advanced solid tumors and hematological malignancies...

BACKGROUND: Extranodal natural killer/T-cell lymphoma (NKTL) is an aggressive type of non-Hodgkin lymphoma with dismal outcome. A better understanding of disease biology and key oncogenic process is necessary for the development of targeted therapy. Super-enhancers (SEs) have been shown to drive pivotal oncogenes in various malignancies. However, the landscape of SEs and SE-associated oncogenes remain elusive in NKTL. METHODS: We used Nano-ChIP-seq of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs NKTL primary tumor samples...

Phosphatases of regenerating liver (PRL-1, PRL-2, PRL-3; also known as PTP4A1, PTP4A2, PTP4A3, respectively) control intracellular magnesium levels by interacting with the CNNM magnesium transport regulators. Still, the exact mechanism governing magnesium transport by this protein complex is not well understood. Herein, we have developed a genetically encoded intracellular magnesium-specific reporter and demonstrate that the CNNM family inhibits the function of the TRPM7 magnesium channel. We show that the small GTPase ARL15 increases CNNM3/TRPM7 protein complex formation to reduce TRPM7 activity...

Protein tyrosine phosphatase type IVA member 3 (PTP4A3 or PRL-3) is a nonreceptor, oncogenic, dual-specificity phosphatase that is highly expressed in many human tumors, including ovarian cancer, and is associated with a poor patient prognosis. Recent studies suggest PTP4A3 directly dephosphorylates SHP-2 phosphatase as part of a STAT3-PTP4A3 feedforward loop and directly dephosphorylates p38 kinase. The goal of the current studies was to examine the effect of a PTP4A phosphatase inhibitor, 7-imino-2-phenylthieno[3,2- c ]pyridine-4,6(5 H ,7 H )-dione or JMS-053, on ovarian cancer STAT3, SHP-2, and p38 kinase phosphorylation...

BACKGROUND: It has been reported that ubiquitin specific peptidase 4 (USP4) was functional in several tumors, but its function and mechanism in gastric cancer were still unknown. METHODS: Bioinformatic tools were used to predict the prognosis of gastric cancer patients and the expression levels of USP4 in gastric cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting were carried out to detect the messenger RNA (mRNA) and protein levels...

Background: A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 ( PTP4A3 /PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC. Methods: We included three LIHC datasets with clinical information and expression profiles from public databases...

[This retracts the article DOI: 10.1016/j.omtn.2019.10.020.].

Objective: To evaluate the clinical correlation of epithelial-mesenchymal transition (EMT) with PRL-3 and MMP9 expression in the circulating tumor cells (CTCs) of patients with colorectal cancer (CRC). Materials and Methods: Between January 2016 and December 2018, the EMT phenotype-based subsets of CTCs and the expression levels of PRL-3 and MMP9 in CTCs were identified, and their clinical values in 172 patients were evaluated. The CTCs were isolated, classified, and counted using the CanPatrol™ CTC filtration system...

The Protein Tyrosine Phosphatase of Regenerating Liver-3, also known as PRL-3 or PTP4A3, is among the most oncogenic known protein tyrosine phosphatases, promoting cell migration, survival, metabolism, angiogenesis, and tumor formation. These diverse cancer-associated phenotypic actions are thought to be mediated at least in part by the unique ability of PTP4A3 to function as a positive signal transducer capable of activating STAT3 and ERK1/2 and deactivating p38 kinase. PTP4A3 is significantly upregulated in a majority of human ovarian cancers and is associated with a poor patient prognosis...

PRL-3 is a tyrosine phosphatase linked with tumor metastasis. It is detected high expression in different kinds of cancers, including colorectal, gastric, ovarian, and liver cancer. Its high expression is positively correlated with the progression of tumors and negatively with survivals of patients. However, the detailed mechanism underlying PRL-3 in tumor metastasis still remains unclear. In the present study, we found that PRL-3 is able to bind to β3-tubulin in pull-down and co-immunoprecipitation assays...

Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases...

The relationship between the checkpoint kinase Chk1 and the STAT3 pathway was examined in multiple myeloma cells. Gene expression profiling of U266 cells exposed to low (nmol/L) Chk1 inhibitor [PF-477736 (PF)] concentrations revealed STAT3 pathway-related gene downregulation (e.g., BCL-XL, MCL-1, c-Myc), findings confirmed by RT-PCR. This was associated with marked inhibition of STAT3 Tyr705 (but not Ser727) phosphorylation, dimerization, nuclear localization, DNA binding, STAT3 promoter activity by chromatin immunoprecipitation assay, and downregulation of STAT-3-dependent proteins...

Hypoxia within the tumor microenvironment, which leads to excessive ROS and genomic instability, is one of the hallmarks of cancer, contributing to self-renewal capability, metastasis, and radio-chemotherapy resistance. PRL-3 is an oncoprotein involved in various pro-survival signaling pathways, such as Ras/Erk, PI3K/Akt, Src/STAT, mTORC1 and JAK/STAT. However, there is little evidence connecting PRL-3-mediated apoptosis resistance to tumor microenvironmental stress. In this study, by profiling the PRL-3 expression of multiple tumor types retrieved from public databases (TCGA and NCBI GEO), we confirmed the oncogenic function of PRL-3 and found an intriguing connection between PRL-3 expression and tumor hypoxia signature genes...

Ras-related GTP binding (Rag) GTPases are required to activate mechanistic target of rapamycin complex 1 (mTORC1), which plays a central role in cell growth and metabolism and is considered as one of the most important oncogenic pathways. Therefore, Rag GTPases have been speculated to play a pro-cancer role via mTOR induction. However, aside from stimulation of mTOR signaling, firm links connecting Rag GTPase activity and their downstream effectors with cancer progression, remain largely unreported. In this study, we reported a novel link between RagB/C and a known oncoprotein phosphatase of regenerating liver-3 (PRL-3) by screening 22 pairs of tumors and their adjacent normal tissues from gastric, liver and lung cancers, and validating our findings in cancer cell lines with ectopic RagB/C expression...