Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer

Mcheik, Soha; Aptecar, Leticia; Coopman, Peter J.; Freiss, Gilles

doi:10.3390/biom10121659

Cited by 22 publications

(21 citation statements)

References 146 publications

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“…S3E). PTPN13 has been shown to be involved in multiple signaling pathways including dephosphorylation of IRS-1 and inhibition of PI3K (16). By comparison, category IIB consisted of 340 phosphosites on 248 proteins that were up-regulated by ligand in IGF1Rexpressing cells significantly greater than in IR-expressing cells.…”

Section: Differential Phosphorylated Patterns By Ir and Igf1r In Ligandmentioning

confidence: 99%

Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

Nagao

Cai

Albrechtsen

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Insulin and insulin-like growth factor 1 (IGF-1) receptors share many downstream signaling pathways but have unique biological effects. To define the molecular signals contributing to these distinct activities, we performed global phosphoproteomics on cells expressing either insulin receptor (IR), IGF-1 receptor (IGF1R), or chimeric IR-IGF1R receptors. We show that IR preferentially stimulates phosphorylations associated with mammalian target of rapamycin complex 1 (mTORC1) and Akt pathways, whereas IGF1R preferentially stimulates phosphorylations on proteins associated with the Ras homolog family of guanosine triphosphate hydrolases (Rho GTPases), and cell cycle progression. There were also major differences in the phosphoproteome between cells expressing IR versus IGF1R in the unstimulated state, including phosphorylation of proteins involved in membrane trafficking, chromatin remodeling, and cell cycle. In cells expressing chimeric IR-IGF1R receptors, these differences in signaling could be mapped to contributions of both the extra- and intracellular domains of these receptors. Thus, despite their high homology, IR and IGF1R preferentially regulate distinct networks of phosphorylation in both the basal and stimulated states, allowing for the unique effects of these hormones on organismal function.

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Section: Differential Phosphorylated Patterns By Ir and Igf1r In Ligandmentioning

confidence: 99%

Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

Nagao

Cai

Albrechtsen

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…The previous article studied the role of PTPN13 in FAS-mediated apoptosis. The interaction of PTPN13 and the FAS (CD95/APO-1) death receptor is reported as the first evidence ( 52 ). In our report, the results showed that PTPN13 expression in normal tissues is lower than that in PAAD tissues, but PTPN13 expression in PAAD patients has nothing related to the tumor stage.…”

Section: Discussionmentioning

confidence: 99%

PTPN2, A Key Predictor of Prognosis for Pancreatic Adenocarcinoma, Significantly Regulates Cell Cycles, Apoptosis, and Metastasis

et al. 2022

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ObjectiveThis study conducted a comprehensive analysis of the members of the PTPN family and emphasized the key role of PTPN2 as a potential therapeutic target and diagnostic biomarker in improving the survival rate of PAAD.MethodOncomine was used to analyze the pan-cancer expression of the PTPN gene family. The Cancer Genome Atlas (TCGA) data as well as Genotype-Tissue Expression (GTEx) data were downloaded to analyze the expression and prognosis of PTPNs. The diagnosis of PTPNs was evaluated by the experimental ROC curve. The protein-protein interaction (PPI) network was constructed by combining STRING and Cytoscape. The genes of 50 proteins most closely related to PTPN2 were screened and analyzed by GO and KEGG enrichment. The differentially expressed genes of PTPN2 were found by RNA sequencing, and GSEA enrichment analysis was carried out to find the downstream pathways and targets, which were verified by online tools and experiments. Finally, the relationship between PTPN2 and immune cell infiltration in PAAD, and the relationship with immune score and immune checkpoint were studied.ResultThe expression patterns and the prognostic value of multiple PTPNs in PAAD have been reported through bioinformatic analyzes. Among these members, PTPN2 is the most important prognostic signature that regulates the progression of PAAD by activating JAK-STAT signaling pathway. Comparison of two PAAD cell lines with normal pancreatic epithelial cell lines revealed that PTPN2 expression was up-regulated as a key regulator of PAAD, which was associated with poor prognosis. Knockdown of PTPN2 caused a profound decrease in PAAD cell growth, migration, invasion, and induced PAAD cell cycle and apoptosis. In addition, we conducted a series of enrichment analyses to investigate the PTPN2-binding proteins and the PTPN2 expression-correlated genes. We suggest that STAT1 and EGFR are the key factors to regulate PTPN2, which are involved in the progression of PAAD. Meanwhile, the silencing of PTPN2 induced the repression of STAT1 and EGFR expression.ConclusionThese findings provide a comprehensive analysis of the PTPN family members, and for PAAD, they also demonstrate that PTPN2 is a diagnostic biomarker and a therapeutic target.

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“…PTPN13 is a tyrosine phosphatase that is frequently downregulated or silenced in several tumors. In addition, it is thought to be an independent prognostic marker for increased overall survival in several cancers [ 54 ]. Further evidence demonstrated that PTPN13 overexpression inhibited cell invasiveness through cell junction stabilization [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration

et al. 2022

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Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-β receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.

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Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer

Cited by 22 publications

References 146 publications

Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

Distinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains

PTPN2, A Key Predictor of Prognosis for Pancreatic Adenocarcinoma, Significantly Regulates Cell Cycles, Apoptosis, and Metastasis

Direct conversion of human umbilical cord mesenchymal stem cells into retinal pigment epithelial cells for treatment of retinal degeneration

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