scholarly journals Mechanism of Protein Tyrosine Phosphatase O Receptor in Hepatocellular Carcinoma

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Ye Qin ◽  
Xinke Xie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Chronic Inflammation ◽  
Protein Tyrosine Phosphatase ◽  
Liver Tumors ◽  
Tyrosine Phosphatase ◽  
Common Type ◽  
Tumor Suppressor Protein ◽  
Protein Tyrosine ◽  
New Type

Pathologist Virchow has proposed a hypothesis that the origin of tumors comes from chronic inflammation. Clinically, liver tumors can be divided into three types Hepatocellular carcinoma (HCC) is the most common type, which is closely related to various kinds of inflammation. Studies have shown that protein tyrosine phosphatase receptor type O (PTPRO) is a new type of protein tyrosine phosphatase, which is negatively correlated with tumorigenesis. As a new tumor suppressor protein, PTPRO is of great significance for the diagnosis and treatment of HCC in the future. This paper aims to discuss the mechanism of PTPRO in HCC.

scholarly journals Research Progress of Protein Tyrosine Phosphatase Receptor-Type O in Hepatocellular Carcinoma

2021 ◽  
Vol 5 (6) ◽  
pp. 94-97
Author(s):  
Xiangzhe Yang ◽  
Ye Qin ◽  
Xinke Xie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Tyrosine Phosphatase ◽  
Malignant Tumors ◽  
Tyrosine Phosphatase ◽  
Basic Research ◽  
Clinical Treatment ◽  
Receptor Type ◽  
Research Progress ◽  
Protein Tyrosine ◽  
New Type

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with a high incidence and has become one of the most malignant cancers worldwide. Its clinical treatment mainly includes surgical intervention, chemotherapy, and immunotherapy, with poor curative effect and prognosis. In recent years, with the development of basic research, it has been revealed that protein tyrosine phosphatase receptor-type O (PTPRO) plays an important role in the pathogenesis of hepatocellular carcinoma. Protein tyrosine phosphatase receptor-type O is a new type of protein tyrosine phosphatase, which has been proven to inhibit oncoprotein. In this paper, the potential mechanism of protein tyrosine phosphatase receptor -type O in the progression of hepatocellular carcinoma is discussed to provide reference for clinical treatment and drug development.

scholarly journals IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000285 ◽  
Author(s):  
Wenjie Zhang ◽  
Yang Liu ◽  
Zhongyi Yan ◽  
Hui Yang ◽  
Wei Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Hepatocellular Carcinoma ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Post Surgery ◽  
Monocytes And Macrophages

BackgroundWe have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC).MethodsThe expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC. The mechanic regulations were studied by using both in vitro and in vivo studies.ResultsWe found a significant decrease in PTPRO in HCC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in HCC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with HCC and were associated with increased T-cell exhaustion (Tim3+T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25–3 p axis. Monocytes and TAMs showed significantly increased miR-25–3 p expression, which could target the 3′ untranslated region of PTPRO. The miR-25–3 p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in HCC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25–3 p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25–3 p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in an orthotopic tumor transplantation model.ConclusionsIncreased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25–3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

scholarly journals Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

2012 ◽  
Vol 11 (1) ◽  
pp. 6 ◽  
Author(s):  
Maria Meehan ◽  
Laavanya Parthasarathi ◽  
Niamh Moran ◽  
Caroline A Jefferies ◽  
Niamh Foley ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Aurora Kinase ◽  
Aurora Kinase A ◽  
Protein Tyrosine ◽  
Neuroblastoma Tumor ◽  
Kinase A

Protein Tyrosine Phosphatase Receptor Type O (PTPRO) Exhibits Tumor Suppressor Properties in K562 Cells by Dephosphorylating Bcr-Abl.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2914-2914
Author(s):  
Sarmila Majumder ◽  
Tasneem Motiwala ◽  
Kalpana Ghoshal ◽  
Huban Kutay ◽  
Jharna Datta ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Protein Tyrosine Phosphatase ◽  
Cpg Island ◽  
Tyrosine Phosphatase ◽  
Ectopic Expression ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Catalytically Active

Abstract Regulation of protein phosphorylation by concerted action of protein kinases and phosphatases is important for normal physiological processes. Altered function or expression of one or more components of these regulatory molecules leads to many pathological conditions including cancer. We have previously shown that the truncated form of the receptor-type protein tyrosine phosphatase PTPROt predominantly expressed in haematopoietic cells is suppressed in Chronic Lymphocytic Leukemia (B-CLL). A direct correlation of CpG island methylation and reduced expression of the gene was observed in primary CLL samples and in several leukemia cell lines. To assess the functional significance of loss of PTPROt function in leukemia, we selected K562 cells as a model system, as PTPROt expression is silenced in these cells and is reactivated upon treatment with DNA hypomethylating agents. Ectopic expression of the catalytically active PTPROt inhibited growth of K562 cells and their clonogenic survival in soft agar (a characteristic of cancer cells). Further, cells expressing PTPROt exhibited delayed entry into S-phase from G0/G1 phase. Induction of apoptosis increased significantly in K562 cells expressing functional phosphatase upon serum withdrawal or exposure to the apoptogenic agent camptothecin. Tumorigenic potential of K562 cells in athymic nude mice was also significantly reduced upon ectopic expression of PTPROt. Finally, we demonstrate that the Bcr-Abl fusion protein, product of abnormal chromosomal translocation [t(9;22)] in chronic myelogenous leukemia, is a substrate of PTPROt. Tyrosine phosphorylation of this potent kinase was markedly reduced in K562 cells expressing the catalytically active PTPROt. Enhanced dephosphorylation of Bcr-Abl by PTPROt both in vivo and in vitro explains the observed phenotypes of the PTPROt expressing K562 cells. These data taken together delineate the molecular mechanism of tumor suppressor function of PTPROt in leukemic cells characterized by Philadelphia chromosome. (This work was supported by a grant CA101956 from the National Institutes of Health).

scholarly journals The Role of the Tumor Suppressor Gene Protein Tyrosine Phosphatase Gamma in Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Christian Boni ◽  
Claudio Sorio
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Protein Tyrosine Phosphatase ◽  
Growth Regulation ◽  
Current Knowledge ◽  
Tyrosine Phosphatase ◽  
Suppressor Gene ◽  
Missense Mutations ◽  
Protein Tyrosine

Members of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell cycle, proliferation, invasion and angiogenesis, they represent key parts of complex physiological homeostatic mechanisms. Protein tyrosine phosphatase gamma (PTPRG) is classified as a R5 of the receptor type (RPTPs) subfamily and is broadly expressed in various isoforms in different tissues. PTPRG is considered a tumor-suppressor gene (TSG) mapped on chromosome 3p14-21, a region frequently subject to loss of heterozygosity in various tumors. However, reported mechanisms of PTPRG downregulation include missense mutations, ncRNA gene regulation and epigenetic silencing by hypermethylation of CpG sites on promoter region causing loss of function of the gene product. Inactive forms or total loss of PTPRG protein have been described in sporadic and Lynch syndrome colorectal cancer, nasopharyngeal carcinoma, ovarian, breast, and lung cancers, gastric cancer or diseases affecting the hematopoietic compartment as Lymphoma and Leukemia. Noteworthy, in Central Nervous System (CNS) PTPRZ/PTPRG appears to be crucial in maintaining glioblastoma cell-related neuronal stemness, carving out a pathological functional role also in this tissue. In this review, we will summarize the current knowledge on the role of PTPRG in various human cancers.

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