Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors

Mei, Wenhan; Wang, Kemin; Huang, Jian; Zheng, Xiujun

doi:10.1371/journal.pone.0166538

Cited by 11 publications

(10 citation statements)

References 25 publications

(38 reference statements)

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“…Liver and lung tumours in LysM-PTP1B -/- mice all stained positively for the myeloid-specific enzyme myeloperoxidase, verifying their myeloid lineage, and thereby suggesting the development of tumours to be similar to previously reported myeloproliferative disorders, with mutations in PTP1B (Figure 1h)(19, 20) .…”

Section: Resultssupporting

confidence: 84%

Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

et al. 2018

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Protein tyrosine phosphatase PTP1B is a critical regulator of signaling pathways controlling metabolic homeostasis, cell proliferation, and immunity. In this study, we report that global or myeloid-specific deficiency of PTP1B in mice decreases lifespan. We demonstrate that myeloid-specific deficiency of PTP1B is sufficient to promote the development of acute myeloid leukemia. LysM-PTP1B mice lacking PTP1B in the innate myeloid cell lineage displayed a dysregulation of bone marrow cells with a rapid decline in population at midlife and a concomitant increase in peripheral blood blast cells. This phenotype manifested further with extramedullary tumors, hepatic macrophage infiltration, and metabolic reprogramming, suggesting increased hepatic lipid metabolism prior to overt tumor development. Mechanistic investigations revealed an increase in anti-inflammatory M2 macrophage responses in liver and spleen, as associated with increased expression of arginase I and the cytokines IL10 and IL4. We also documented STAT3 hypersphosphorylation and signaling along with JAK-dependent upregulation of antiapoptotic proteins Bcl2 and BclXL. Our results establish a tumor suppressor role for PTP1B in the myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia. This study defines a tumor suppressor function for the protein tyrosine phosphatase PTP1B in myeloid lineage cells, with evidence that its genetic inactivation in mice is sufficient to drive acute myeloid leukemia. .

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Section: Resultssupporting

confidence: 84%

Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

et al. 2018

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“…Finally, one STAT3 wildtype patient (BALCL11) had a novel sequence variant detected in PTPN1 (Thr263Ile). PTPN1 encodes PTP1B which dephosphorylates tyrosine residues and through this mechanism is involved in regulation of intracellular signalling pathways including the JAK/STAT pathway [ 15 ]. This variant causes a change in an amino acid which is critical for protein function and is predicted to be deleterious by multiple in silico predictors [ 16 ].…”

Section: Resultsmentioning

confidence: 99%

Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma

et al. 2018

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Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of T-cell lymphoma that occurs after implantation of breast prostheses. We performed comprehensive next generation sequencing based genomic characterization of 11 cases of BIA-ALCL including sequence variant detection on 180 genes frequently mutated in haematological malignancy, genome-wide copy number assessment, structural variant detection involving the T-cell receptor loci and TRB deep-sequencing. We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients. We also observed germline TP53 mutations in two cases. In addition we detected a recurrent copy number loss involving RPL5 as well as copy number amplifications involving TNFRSF11A [RANK] (in 2 cases), MYC, P2RX7, TMEM119 and PDGFRA. In summary, our comprehensive genomic characterisation of 11 cases of BIA-ALCL has provided insight into potential pathobiological mechanisms (JAK/STAT, MYC and TP53) as well as identifying targets for future therapeutic intervention (TNFRSF11A, PDGFRA) in this rare entity.

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“…Importantly, the splice variant PTP1BΔE6, which is expressed in colon and thyroid tumors, lacks phosphatase activity. However, its expression induced transformation of rat fibroblasts without Src activation, indicating that it is involved in signaling pathways independent of Src [ 76 ].…”

Section: Ptp1b In Cancermentioning

confidence: 99%

Recent advances in PTP1B signaling in metabolism and cancer

2021

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Protein tyrosine phosphorylation is one of the major post-translational modifications in eukaryotic cells and represents a critical regulatory mechanism of a wide variety of signaling pathways. Aberrant protein tyrosine phosphorylation has been linked to various diseases, including metabolic disorders and cancer. Few years ago, protein tyrosine phosphatases (PTPs) were considered as tumor suppressors, able to block the signals emanating from receptor tyrosine kinases. However, recent evidence demonstrates that misregulation of PTPs activity plays a critical role in cancer development and progression. Here, we will focus on PTP1B, an enzyme that has been linked to the development of type 2 diabetes and obesity through the regulation of insulin and leptin signaling, and with a promoting role in the development of different types of cancer through the activation of several pro-survival signaling pathways. In this review, we discuss the molecular aspects that support the crucial role of PTP1B in different cellular processes underlying diabetes, obesity and cancer progression, and its visualization as a promising therapeutic target.

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Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors

Cited by 11 publications

References 25 publications

Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

Deficiency in Protein Tyrosine Phosphatase PTP1B Shortens Lifespan and Leads to Development of Acute Leukemia

Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma

Recent advances in PTP1B signaling in metabolism and cancer

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