Inhibition of SHP2 leads to mesenchymal to epithelial transition in breast cancer cells

Xd, Zhou; Agazie, YM

doi:10.1038/cdd.2008.54

Cited by 85 publications

(95 citation statements)

References 38 publications

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“…Genetic and biochemical studies in recent years have suggested that SHP2 plays a broad role not only in cell proliferation [12], survival [13], and differentiation [14], but also in development [15,16] and tumorigenesis [17][18][19] of malignancies via Ras/Erk [20], PI3K/Akt [21] and other signaling pathways. In accordance to a recent study [18], our previous studies [22][23][24] have demonstrated that SHP2 plays a crucial role in breast oncogenesis. Recently, we have also found for the first time that SHP2 is widely expressed by lung cancer cells, and that the high expression of SHP2 may promote the invasion and metastasis of NSCLC through angiogenesis and the lymphatic system [25,26].…”

Section: Introductionsupporting

confidence: 63%

“…Shp2 was reported to be a modulator that prolongs the activation of Erk [18,20,22], which suggests its role in carcinogenesis and development of several kinds of malignancies. Furthermore, Lima et al [36] reported that insulininduced IRS-1/SHP2 complex was associated with insulin resistance and played a role in the control of AKT phosphorylation in an animal model.…”

Section: Shp2 Is Upstream Of Ras and Pi3k Pathways And Plays A Importmentioning

confidence: 99%

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The Tyrosine Phosphatase SHP2: A Key Molecule Linked both Type 2 Diabetes and Cancers?

Luo¹,

Tang²,

Yang³

et al. 2014

Med chem

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Emerging epidemiological evidence suggests that T2DM may be associated with an increased risk of certain cancers. However, the underlying molecular mechanism linked these two diseases remains largely unknown. SHP2, a non-receptor protein tyrosine phosphatase encoded by pro-oncogene PTPN11, has been reported involved in insulin resistance through PI3K/Akt/mOTR signaling and has also been considered to play a vital role in carcinogenesis via Ras/Erk pathways. Based on our previous studies, we hypothesize that SHP2 may present a key molecule linked both T2DM and cancers through both Ras/Erk and PI3K/AKT/mTOR signaling pathways. We believe that the comprehensive and detailed investigation of SHP2 may provide a new insight into the underlying molecular mechanism linked both T2DM and cancers, thereby facilitating the process to discover novel therapeutic targets to prevent and treat cancers.

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Section: Introductionsupporting

confidence: 63%

Section: Shp2 Is Upstream Of Ras and Pi3k Pathways And Plays A Importmentioning

confidence: 99%

The Tyrosine Phosphatase SHP2: A Key Molecule Linked both Type 2 Diabetes and Cancers?

Luo¹,

Tang²,

Yang³

et al. 2014

Med chem

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“…Inhibition of SHP2 suppressed EGF-induced activation of the Ras extracellular signalregulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways in breast cancer cell lines, induced epithelial cell morphology, and led to reversion to a normal breast epithelial phenotype (40). Furthermore, E-cadherin was upregulated, and fibronectin and vimentin were downregulated (40). These data suggest that ERK also plays an important role in the process of MET (Fig.…”

Section: Mechanism Of Metmentioning

confidence: 67%

“…As noted above, the activity of Akt in breast carcinoma was shown to be repressed during MET, suggesting that repression of Akt activity may be related to MET (40). It was also shown that MET induced by BMP2 in mesenchymal colon carcinoma cells (CT26; ref.…”

Section: Mechanism Of Metmentioning

confidence: 84%

“…In addition, Src homology phosphotyrosine phosphatase 2 (SHP2), which possesses 2 in tandem arranged Src homology 2 domains (a common target of receptor tyrosine kinases) in the N-terminal region (39), seem to play an important role in the EGF system. Inhibition of SHP2 suppressed EGF-induced activation of the Ras extracellular signalregulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways in breast cancer cell lines, induced epithelial cell morphology, and led to reversion to a normal breast epithelial phenotype (40). Furthermore, E-cadherin was upregulated, and fibronectin and vimentin were downregulated (40).…”

Section: Mechanism Of Metmentioning

confidence: 99%

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Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

Yao

Dai

Peng

2011

Molecular Cancer Research

384

296

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Cancer metastasis consists of a sequential series of events, and the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are recognized as critical events for metastasis of carcinomas. A current area of focus is the histopathological similarity between primary and metastatic tumors, and MET at sites of metastases has been postulated to be part of the process of metastatic tumor formation. Here, we summarize accumulating evidence from experimental studies that directly supports the role of MET in cancer metastasis, and we analyze the main mechanisms that regulate MET or reverse EMT in carcinomas. Given the critical role of MET in metastatic tumor formation, the potential to effectively target the MET process at sites of metastasis offers new hope for inhibiting metastatic tumor formation.

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Protein Tyrosine Phosphatase Expression Profile of Rheumatoid Arthritis Fibroblast‐like Synoviocytes: A Novel Role of SH2 Domain–Containing Phosphatase 2 as a Modulator of Invasion and Survival

Stanford¹,

Maestre²,

Campbell³

et al. 2013

Arthritis & Rheumatism

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OBJECTIVE The fibroblast-like synoviocytes (FLS) in the synovial intimal lining of the joint are key mediators of inflammation and joint destruction in rheumatoid arthritis (RA). In RA, these cells aggressively invade the extracellular matrix, producing cartilage-degrading proteases and inflammatory cytokines. The behavior of FLS is controlled by multiple interconnected signal transduction pathways involving reversible phosphorylation of proteins on tyrosine residues. However, little is known about the role of the protein tyrosine phosphatases (PTPs) in FLS function. The objective of this study was to explore the expression of all the PTP genes (PTPome) in FLS. METHODS A comparative screening was conducted of the expression of the PTPome in FLS from patients with RA or osteoarthritis (OA). The functional effect of a PTP up-regulated in RA, SHP-2, was then analyzed by knock-down using cell-permeable antisense oligonucleotides in RA FLS. RESULTS PTPN11 was over-expressed in RA compared to OA FLS. Knock-down of PTPN11, which encodes SHP-2, using a cell-permeable antisense oligonucleotide, decreased the invasion, migration, adhesion, spreading and survival of RA FLS. Additionally, signaling in response to growth factors and inflammatory cytokines was impaired by the knock-down of SHP-2. RA FLS deficient in SHP-2 displayed decreased activation of focal adhesion kinase and mitogen-activated protein kinases. CONCLUSION These findings indicate a novel role for SHP-2 in mediating human FLS function, and suggest that SHP-2 promotes the invasiveness and survival of RA FLS. Further investigation may reveal SHP-2 to be a candidate therapeutic target for RA.

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Inhibition of SHP2 leads to mesenchymal to epithelial transition in breast cancer cells

Cited by 85 publications

References 38 publications

The Tyrosine Phosphatase SHP2: A Key Molecule Linked both Type 2 Diabetes and Cancers?

The Tyrosine Phosphatase SHP2: A Key Molecule Linked both Type 2 Diabetes and Cancers?

Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation

Protein Tyrosine Phosphatase Expression Profile of Rheumatoid Arthritis Fibroblast‐like Synoviocytes: A Novel Role of SH2 Domain–Containing Phosphatase 2 as a Modulator of Invasion and Survival

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