The role of receptor‐type protein tyrosine phosphatases in cancer

Lv, Zhengyuan; Wang, Tianming; Cao, Xin; Sun, Mengting; Qu, Yuan

doi:10.1002/prm2.12090

Cited by 3 publications

(5 citation statements)

References 134 publications

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“…RNU2-57P, RNU2-29P, RNU2-3P, RNU2-7P, and RNU2-33P are all part of this snRNA family and were also downregulated in responders. Moreover, high expression of PTPRR, which is involved in this pathway, has been described in several types of cancer [33]. Other significant small RNAs at T2 in our study are backed by the literature.…”

Section: Discussionsupporting

confidence: 71%

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer

Zafra,

Onieva,

Oliver

et al. 2024

IJMS

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Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)—complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease.

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Section: Discussionsupporting

confidence: 71%

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer

Zafra,

Onieva,

Oliver

et al. 2024

IJMS

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“…Transcriptome analysis indicated downregulation of “phosphorylation” processes (p value 1.05e-12) in MDEOs (Figure 2G). This was associated with increased expression levels of several receptor-type tyrosine-protein phosphatases (PTPRU, PTPRM and PTPRS) reported to regulate the HIPPO/YAP and ERK signaling cascades (20, 21) (Figure 2G, Figure S2B). Altogether, these in silico studies suggested dysregulated signal transduction in the duodenal epithelium of MASH patients as compared to healthy subjects.…”

Section: Resultsmentioning

confidence: 98%

Duodenal organoids from metabolic dysfunction-associated steatohepatitis patients exhibit altered digestive homeostasis

Hadefi,

Leprovots,

Dinsart

et al. 2024

Preprint

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Background and AimsMetabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research underscores the importance of the gut-liver axis in its pathogenesis, an aspect less explored in human studies. Here, we investigated whether the duodenal epithelium of MASH patients, could exhibit intrinsic dysfunctions.MethodsDuodenal epithelial organoids were generated from 16 MASH patients and 14 healthy controls. Biopsies and patient-derived organoid transcriptomes were then analyzed to evaluate if specific intestinal pathways were differentially modulated in MASH subjects. Functional assays were performed to assess the duodenal epithelial digestive potential and barrier functionality.ResultsOrganoid formation efficiency was similar between control-derived epithelial organoids (CDEOs) and MASH-derived epithelial organoids (MDEOs) (71% and 69%, respectively). Despite global heterogeneity in growth patterns, MDEOs frequently exhibited cystic spheroid morphology. MDEOs displayed altered digestive homeostasis associated with reduced mature absorptive cell fate, but they retained their lipid metabolic capacity, possibly mediated by lipid oxidation in stem/progenitor cells. Additionally, MDEOs misexpressed components of tight and adherens junctions and desmosomes compared to controls. However, MDEOs maintained pore and leak pathway integrity, indicating that the duodenal epithelial barrier remained functionally preserved under tested conditions.ConclusionsThis study provides evidence that the duodenal epithelium of MASH patients exhibits significant alterations in its digestive and barrier functions. This study sheds light on the intricate dynamics of duodenal epithelial alterations in MASH, highlighting potential therapeutic avenues for restoring intestinal homeostasis.

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“…Markedly decreased protein levels of PTPRJ have been observed in cancer cell lines (e.g., colon, breast, pancreas, thyroid, and lung), suggesting the tumor-suppressive role of PTPRJ [249]. However, significantly higher upregulation of PTPRJ has been identified in glioblastoma multiforme, indicating a potentially cancerspecific function of PTPRJ [249,250]. PTPRJ plays a negative role in regulating EC growth by inhibiting VEGF-dependent ERK1/2 activation [251,252].…”

Section: Protein Tyrosine Phosphatase Receptor Type J (Ptprj)/density...mentioning

confidence: 99%

“…In gastric cancer, PTPRJ inhibits malignant transformation by dephosphorylating EGFR and blocking the mitogen-activated protein kinase (MEK)/ERK and PI3K/Akt pathways. In cervical cancer cell lines, PTPRJ inactivates the Janus kinase 1 (JAK1)/STAT3 pathway, impeding proliferation and tumor formation [250]. Soluble TSP-1 binds to the extracellular domain of PTPRJ, enhancing its catalytic activity and inhibiting cell growth.…”

Section: Protein Tyrosine Phosphatase Receptor Type J (Ptprj)/density...mentioning

confidence: 99%

“…Several studies have confirmed PTPRJ-mediated Src activation. PTPRJ dephosphorylates the inhibitory Tyr residue of Src, leading to Src auto-phosphorylation and full activation, which can initiate tumor-associated angiogenesis [250][251][252]254]. A short variant of PTPRJ, named sPTPRJ, is generated by alternative splicing, resulting in a soluble protein secreted into the supernatant by both endothelial and tumor cells.…”

Section: Protein Tyrosine Phosphatase Receptor Type J (Ptprj)/density...mentioning

confidence: 99%

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Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity

Fonódi,

Nagy,

Boratkó

2024

IJMS

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Tumor angiogenesis, the formation of new blood vessels to support tumor growth and metastasis, is a complex process regulated by a multitude of signaling pathways. Dysregulation of signaling pathways involving protein kinases has been extensively studied, but the role of protein phosphatases in angiogenesis within the tumor microenvironment remains less explored. However, among angiogenic pathways, protein phosphatases play critical roles in modulating signaling cascades. This review provides a comprehensive overview of the involvement of protein phosphatases in tumor angiogenesis, highlighting their diverse functions and mechanisms of action. Protein phosphatases are key regulators of cellular signaling pathways by catalyzing the dephosphorylation of proteins, thereby modulating their activity and function. This review aims to assess the activity of the protein tyrosine phosphatases and serine/threonine phosphatases. These phosphatases exert their effects on angiogenic signaling pathways through various mechanisms, including direct dephosphorylation of angiogenic receptors and downstream signaling molecules. Moreover, protein phosphatases also crosstalk with other signaling pathways involved in angiogenesis, further emphasizing their significance in regulating tumor vascularization, including endothelial cell survival, sprouting, and vessel maturation. In conclusion, this review underscores the pivotal role of protein phosphatases in tumor angiogenesis and accentuate their potential as therapeutic targets for anti-angiogenic therapy in cancer.

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The role of receptor‐type protein tyrosine phosphatases in cancer

Cited by 3 publications

References 134 publications

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer

Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer

Duodenal organoids from metabolic dysfunction-associated steatohepatitis patients exhibit altered digestive homeostasis

Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity

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