High expression of PTPN21 in B-cell non-Hodgkin’s gastric lymphoma, a positive mediator of STAT5 activity

Plani-Lam, Janice Hiu-Chor; Chow, Tai-Cheong; Fan, Y-H. H.; García-Bloj, Benjamin; Cheng, Lan; Jin, Dong-Yan; Hancock, William S.; Fanayan, Susan; Ingley, Evan; Song, You‐Qiang

doi:10.1038/bcj.2015.107

Cited by 12 publications

(11 citation statements)

References 11 publications

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“…PTPN14 is a well-known tumor suppressor, and our previous study demonstrated that E7 binding-defective mutations remarkably enhance the ability of PTPN14 to delay HeLa cell proliferation, migration, and invasion ( Yun et al, 2019 ). On the other hand, the physiological function of PTPN21 in cervical cancer development is not yet clearly understood, although PTPN21 was reported to be upregulated in several particular cancer types, such as B-cell non-Hodgkin’s gastric lymphoma and bladder cancer ( Carlucci et al, 2010 ; Plani-Lam et al, 2016 ). Unlike PTPN14, PTPN21 exhibited a proteasomal degradation-evasive character, and E7-binding capability did not notably affect its protein level ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study also revealed that PTPN21 or PTPD1 can directly interact with CR3 of HPV18 E7 ( Yun et al, 2019 ), consistent with previous systematic proteomic analyses ( Rozenblatt-Rosen et al, 2012 ; White et al, 2012 ). However, unlike PTPN14, which is defined as a tumor suppressor and particularly controls the Hippo signaling pathway ( Huang et al, 2013 ; Liu et al, 2013 ; Mello et al, 2017 ; Michaloglou et al, 2013 ; Wilson et al, 2014 ), PTPN21 is known to be upregulated in several types of cancer cells and is associated with EGFR activation and intracellular trafficking, implying that this protein might be potentially oncogenic rather than tumor-suppressive ( Carlucci et al, 2010 ; Plani-Lam et al, 2016 ; Roda-Navarro and Bastiaens, 2014 ; Wu et al, 2010 ). While the association between p53 and PTPN21 remains elusive, PTPN21 was reported to inhibit nuclear factor-κB transcriptional activity ( Cho et al, 2017 ), which is known to play a pivotal role in immune responses and be negatively regulated by p53 ( Carra et al, 2020 ; Jang et al, 2020 ; Pal et al, 2014 ; Schneider et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18

Lee

Jin

Shin

et al. 2021

Molecules and Cells

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Human papillomaviruses (HPVs) cause cellular hyper proliferationassociated abnormalities including cervical cancer. The HPV genome encodes two major viral oncoproteins, E6 and E7, which recruit various host proteins by direct interaction for proteasomal degradation. Recently, we reported the structure of HPV18 E7 conserved region 3 (CR3) bound to the protein tyrosine phosphatase (PTP) domain of PTPN14, a welldefined tumor suppressor, and found that this intermolecular interaction plays a key role in E7driven transformation and tumorigenesis. In this study, we carried out a molecular analysis of the interaction between CR3 of HPV18 E7 and the PTP domain of PTPN21, a PTP protein that shares high sequence homology with PTPN14 but is putatively oncogenic rather than tumorsuppressive. Through the combined use of biochemical tools, we verified that HPV18 E7 and PTPN21 form a 2:2 complex, with a dissociation constant of 5 nM and a nearly identical binding manner with the HPV18 E7 and PTPN14 complex. Nevertheless, despite the structural similarities, the biological consequences of the E7 interaction were found to differ between the two PTP proteins. Unlike PTPN14, PTPN21 did not appear to be subjected to proteasomal degradation in HPV18positive HeLa cervical cancer cells. Moreover, knockdown of PTPN21 led to retardation of the migration/invasion of HeLa cells and HPV18 E7expressing HaCaT keratinocytes, which reflects its protumor activity. In conclusion, the associations of the viral oncoprotein E7 with PTPN14 and PTPN21 are similar at the molecular level but play different physiological roles.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18

Lee

Jin

Shin

et al. 2021

Molecules and Cells

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“…PTPN11 was suggested to impact the tumorigenesis and metastasis of CRC [31] and termed as a potential prognostic marker [32]. The data in one report showed that in patients with gastric B cell non-Hodgkin's lymphoma, PTPN21 is over expressed [33]. In ESCA, the expression levels of PTPN1, PTPN4, and PTPN12 were increased.…”

Section: Discussionmentioning

confidence: 99%

The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers

Chen

Yuan

et al. 2020

Cancer Cell Int

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Background: Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers. Methods: Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene-gene interaction network was performed by GeneMA-NIA and the protein-protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed. Results: Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC. Conclusions: Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated

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“…PTPN11 was also suggested to impact the tumorigenesis and metastasis of CRC (30) and termed as a potential prognostic marker (31). The data in one report showed that in patients with gastric B-cell non-Hodgkin's lymphoma, PTPN21 is over expressed (32). In ESCA, the expression levels of PTPN1, PTPN4, and PTPN12 were increased.…”

Section: Discussionmentioning

confidence: 99%

The expression patterns and the prognostic roles of PTPN family members in digestive tract cancers

Chen

Yuan

Jing

2020

Preprint

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Background Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members and the prognosis of digestive tract cancers. Method Expression profiling of PTPN family genes in digestive tract cancers were analyzed through ONCOMINE and UALCAN. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMANIA and the protein–protein interaction (PPI) network was built using STRING portal couple with Cytoscape. Data from The Cancer Genome Atlas (TCGA) were downloaded for validation and to explore the relationship of the PTPN expression with clinicopathological parameters and survival of digestive tract cancers. Results Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. For esophageal carcinoma (ESCA), expression of PTPN1, PTPN4 and PTPN12 were upregulated; expression of PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), expression of PTPN2, PTPN12 and PTPN22 was upregulated in cancer tissue; pathological grade was significantly correlated with PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 was associated with worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colon adenocarcinoma (COAD), expression of PTPN1, PTPN11, PTPN12 and PTPN13 was upregulated, while expression of PTPN18, PTPN21 and PTPN22 was decreased; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression were associated with increased hazards of death. For rectum adenocarcinoma (READ), expression of PTPN12 was upregulated while PTPN21 and PTPN22 were downregulated. Conclusion Members of PTPN family were differently expressed in digestive tract cancers and matched normal tissues. Correlation were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in all of the ESCA, STAD, COAD and READ. PTPN5 was associated with the clinical features and prognosis of both STAD and COAD.

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High expression of PTPN21 in B-cell non-Hodgkin’s gastric lymphoma, a positive mediator of STAT5 activity

Cited by 12 publications

References 11 publications

Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18

Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18

The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers

The expression patterns and the prognostic roles of PTPN family members in digestive tract cancers

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