Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer

Zhang, Bing-Dong; Li, Yuerui; Ding, Lidan; Wang, Yinyin; Liu, Hongyi; Jia, Baoqing

doi:10.1111/cas.14031

Cited by 20 publications

(13 citation statements)

References 18 publications

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“… 23 In addition, different PTPs exert different functions in CRC. Specifically, PTPN4, 31 PTPN9, 32 and PTPRT 33 act as tumor suppressors in CRC, while PTPN2 34 can promote tumor development. Nevertheless, very limited studies have been done about the role of PTPN18 in CRC.…”

Section: Discussionmentioning

confidence: 99%

PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis

Huang

et al. 2021

Genes & Diseases

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Protein tyrosine phosphatase non-receptor type 18 (PTPN18) is often highly expressed in colorectal cancer (CRC), but its role in this disease remains unclear. We demonstrated that PTPN18 overexpression promotes growth and tumorigenesis in CRC cells and that PTPN18 deficiency yields the opposite results in vitro . Moreover, a xenograft assay showed that PTPN18 deficiency significantly inhibited tumorigenesis in vivo . PTPN18 activated the MYC signaling pathway and enhanced CDK4 expression, which is tightly associated with the cell cycle and proliferation in cancer cells. Finally, we found that MYC interacted with PTPN18 and increased the protein level of MYC. In conclusion, our results suggest that PTPN18 promotes CRC development by stabilizing the MYC protein level, which in turn activates the MYC-CDK4 axis. Thus, PTPN18 could be a novel therapeutic target in the future.

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Section: Discussionmentioning

confidence: 99%

PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis

Huang

et al. 2021

Genes & Diseases

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“…It is involved in various biological processes such as T-cell signalling, learning, spatial memory and cerebellar synaptic plasticity Kina et al (2007), Kohda et al (2013), Young et al (2008). PTPN4 also regulates cell proliferation and presents an anti-apoptotic function , Préhaud et al (2010), Zhou et al (2013), Zhang et al (2019). PTPN4 is a large modular protein containing a N-terminal FERM (Band 4.1, Ezrin, radixin, and Moesin) domain, a PDZ (PSD-95/Dlg/ZO-1) domain and a C-terminal catalytic tyrosine phosphatase domain.…”

Section: Introductionmentioning

confidence: 99%

Automatic Bayesian Weighting for SAXS Data

Spill

Karami

Maisonneuve

et al. 2021

Front. Mol. Biosci.

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Small-angle X-ray scattering (SAXS) experiments are important in structural biology because they are solution methods, and do not require crystallization of protein complexes. Structure determination from SAXS data, however, poses some difficulties. Computation of a SAXS profile from a protein model is expensive in CPU time. Hence, rather than directly refining against the data, most computational methods generate a large number of conformers and then filter the structures based on how well they satisfy the SAXS data. To address this issue in an efficient manner, we propose here a Bayesian model for SAXS data and use it to directly drive a Monte Carlo simulation. We show that the automatic weighting of SAXS data is the key to finding optimal structures efficiently. Another key problem with obtaining structures from SAXS data is that proteins are often flexible and the data represents an average over a structural ensemble. To address this issue, we first characterize the stability of the best model with extensive molecular dynamics simulations. We analyse the resulting trajectories further to characterize a dynamic structural ensemble satisfying the SAXS data. The combination of methods is applied to a tandem of domains from the protein PTPN4, which are connected by an unstructured linker. We show that the SAXS data contain information that supports and extends other experimental findings. We also show that the conformation obtained by the Bayesian analysis is stable, but that a minor conformation is present. We propose a mechanism in which the linker may maintain PTPN4 in an inhibited enzymatic state.

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“…In bile cancer, PTPN3 is an oncoprotein that can stimulate cell proliferation, invasion and poor prognosis ( 42 ). PTPN4 is a tumor suppressor that dephosphorylates the Tyr705 residue from p-STAT3 instead of Ser727, resulting in the inhibition of the transcriptional activity of STAT3 ( 43 ). The activation of PTPN5 inhibits the MAPK signaling pathway induced by EGF in breast cancer cells.…”

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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Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer

Cited by 20 publications

References 18 publications

PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis

PTPN18 promotes colorectal cancer progression by regulating the c-MYC-CDK4 axis

Automatic Bayesian Weighting for SAXS Data

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

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