Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia

Xu, Rongzhen

doi:10.1038/cr.2007.18

Cited by 15 publications

(13 citation statements)

References 10 publications

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“…22 Dysregulation of SHP2 signaling is associated with the transformation of blood disorders, including hematologic malignancies. 33,36 Our results here show that SHP2 signaling was required for the survival and progression of GC lymphomas but not of non-GC lymphomas. Our work has also led to the discovery of a SHP2-dependent GC lymphoma proliferative signature comprising a set of genes that are overexpressed in GC lymphomas.…”

Section: Discussionmentioning

confidence: 65%

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Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma

Jiang

Guo

et al. 2014

Haematologica

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Section: Discussionmentioning

confidence: 65%

“…34,35 Overexpression of SHP2 is also detected in samples from patients with leukemia and diffuse large B-cell lymphoma. [36][37][38] However, the relative expression and functional impact of SHP2 in B-cell lymphomagenesis remains unknown.…”

Section: Critical Role Of Shp2 (Ptpn11) Signaling In Germinal Center-mentioning

confidence: 99%

Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma

Jiang

Guo

et al. 2014

Haematologica

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“…Though, PTPs not only lose its function but also has "positive" mechanism in signalling pathways and cell functions, such hyperactive PTPs are Src homology region 2 domain-containing phosphatase-1 (PTPN11) a kenned oncogene along with sundry mutants present in several forms of leukemia [19]. CDC25, a rate-limiting enzyme for cyclin-dependent kinase (CDK)-dependent transition from G1/S phase and G2/M phase in cell cycle, those CDK expression level is more in various cancer cells [20].…”

Section: Gain/loss Of Function Of Ptp Towards Cancermentioning

confidence: 99%

Protein Tyrosine Phosphatase-Prospective Target against Cancer: A Mini Review

Kanagarethinam¹,

Mahapatra²,

Jabalia³

et al. 2017

Cancer Surg

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Contemporary quantum leap on functional characterization of Protein Tyrosine Phosphatase (PTP) superfamily provides an incipient perspective on regulating signal transduction. PTPs are required in the regulation of several cellular processes; especially under stressed and pathogenic conditions leading to sundry human diseases. Concrete inhibition of PTP by oxyanions and active-site directed inhibitors (alkylating agents) may provide implements for human disease treatment involving them. The physiological paramountcy for the advancement of Protein Tyrosine Phosphatase, Non-receptor Type 1 (PTP1B) -predicated therapeutics is a prominent target for diabetes and inordinate corpulence treatment. PTPs are exhilarating quarry for active-site-mediated inhibitors generation. There, proneness to oxidation often create problem on high throughput screens, further the propensity for highly charged potent inhibitors, like non-hydrolysable pTyr mimetics, test with reverence to bioavailability. Subsequent preliminary concerns about specificity and quandaries with deference to hydrophilicity of phosphormimetics, promising successes attained by structure-predicated drug design, mainly the one exploit identical surface topology circumventing the catalytic pocket of each PTP. In PTP1B, it was found that a particular pTyr binding site could be habituated to succeed highly concrete bidentate inhibitors that bind both sites. This conventional approach can avail us to target highly categorical and efficacious inhibitors. Tyrosine phosphorylation increases 1-2% of total protein phosphorylation in tumorigenic transformation or magnification factor simulation essential for a controlled cellular event. This event is controlled by two molecular switches of enzymes protein tyrosine kinase and protein tyrosine phosphatase. Eccentric tyrosine phosphorylation is considered as one of the hallmarks of cancer. PTP has been recommended as next generation drug targets and a sum of PTP have been embroiled in sundry human disease, like cancer. The catalytic mechanism of PTP was demystified by site-directed mutagenesis then kinetic analyses with structural information. They have loss/ gain of function in cancer signaling events leading to dearth of inhibitors to control gain of function including modification of loss of function of PTP cognate genes. This review is about the consequentiality of tyrosine phosphatase enzyme and its role in the mundane cellular event and how it modifies the active site to agonise substrate and alter its action ultimately leading to tumorigenesis.

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“…However, the role of SHP2 in tumorigenesis remains controversial. SHP2 has been suggested to function as an oncogene by several studies (Aceto et al, 2012;Matozaki et al, 2009;Xu, 2007) and as a tumor suppressor by others (Bard-Chapeau et al, 2011). Several cellular proteins have been shown to be substrates of SHP2, including Src (Peng and Cartwright, 1995), focal adhesion kinase (FAK; Tsutsumi et al, 2006), paxillin (Ren et al, 2004), and Gab1 (Montagner et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Protein tyrosine phosphatase SHP2 suppresses podosome rosette formation in Src-transformed fibroblasts

Pan

Cho

Lee³

et al. 2013

Journal of Cell Science

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SummaryPodosomes are actin-enriched membrane protrusions that play important roles in extracellular matrix degradation and invasive cell motility. Podosomes undergo self-assembly into large rosette-like structures in Src-transformed fibroblasts, osteoclasts and certain highly invasive cancer cells. Several protein tyrosine kinases have been shown to be important for the formation of podosome rosettes, but little is known regarding the role of protein tyrosine phosphatases in this process. We found that knockdown of the Src homolog domain-containing phosphatase 2 (SHP2) significantly increased podosome rosette formation in Src-transformed fibroblasts. By contrast, SHP2 overexpression suppressed podosome rosette formation in these cells. The phosphatase activity of SHP2 was essential for the suppression of podosome rosette formation. SHP2 selectively suppressed the tyrosine phosphorylation of Tks5, a scaffolding protein required for podosome formation. The inhibitory effect of SHP2 on podosome rosette formation was associated with the increased activation of Rho-associated kinase (ROCK) and the enhanced polymerization of vimentin filaments. A higher content of polymerized vimentin filaments was correlated with a lower content of podosome rosettes. Taken together, our findings indicate that SHP2 serves as a negative regulator of podosome rosette formation through the dephosphorylation of Tks5 and the activation of ROCK-mediated polymerization of vimentin in Src-transformed fibroblasts.

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Shp2, a novel oncogenic tyrosine phosphatase and potential therapeutic target for human leukemia

Cited by 15 publications

References 10 publications

Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma

Critical role of SHP2 (PTPN11) signaling in germinal center-derived lymphoma

Protein Tyrosine Phosphatase-Prospective Target against Cancer: A Mini Review

Protein tyrosine phosphatase SHP2 suppresses podosome rosette formation in Src-transformed fibroblasts

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