Up-regulation of the protein tyrosine phosphatase SHP-1 in human breast cancer and correlation withGRB2 expression

Yip, Sonia S.; Crew, A. Jayne; Gee, Julia Margaret Wendy; Hui, Rina; Blamey, R.W.; Robertson, J. F. R.; Nicholson, Robert Ian; Sutherland, Robert L.; Daly, Roger J.

doi:10.1002/1097-0215(20001101)88:3<363::aid-ijc7>3.0.co;2-4

Cited by 59 publications

(16 citation statements)

References 36 publications

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“…Deregulation of this pathway has been previously implicated in the promotion of oncogenic phenotypes, including tumorigenesis, invasion, metastasis, proliferation, survival, angiogenesis, anti-apoptosis and immune evasion 7,8 . In breast cancer, the JAK-STAT pathway has been shown to be altered by the following mechanisms: 1) downregulation of phosphotyrosine specific phosphatases 9–11 , 2) elevation of the JAK/STAT-activating ligand IL-6 12–14 , 3) activation of other upstream oncogenic pathways, such as ErbB1, c-Src 15 or PI3K/mTOR 16 , and 4) down-regulation of STAT3 negative regulators such as suppressor of cytokine signaling-3 (SOCS3) 17 .…”

Section: Introductionmentioning

confidence: 99%

Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence

et al. 2016

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Amplifications at 9p24 have been identified in breast cancer and other malignancies, but the genes within this locus casually associated with oncogenicity or tumor progression remain unclear. Targeted next-generation sequencing of post-chemotherapy triple-negative breast cancers (TNBC) identified a group of 9p24-amplified tumors, which contained focal amplification of the Janus kinase-2 (JAK2) gene. These patients had markedly inferior recurrence-free and overall survival compared to patients with TNBC without JAK2 amplification. Presence of JAK2/9p24 amplifications occurred at higher rates in chemotherapy-treated TNBCs than in untreated TNBCs or basal-like breast cancers, or in other subtypes. Similar rates of JAK2 amplification were confirmed in patient-derived TNBC xenografts. In patients where longitudinal specimens were available, JAK2 amplification was selected for during neoadjuvant chemotherapy and eventual metastatic spread, suggesting a role in tumorigenicity and chemoresistance, phenotypes often attributed to a cancer stem-like cell population. In TNBC cell lines with JAK2 copy gains or amplification, specific inhibition of JAK2-STAT6 signaling reduced mammosphere formation and cooperated with chemotherapy in reducing tumor growth in vivo. In these cells, inhibition of JAK1-STAT3 signaling had little effect or, in some cases, counteracted JAK2-specific inhibition. Collectively, these results suggest that JAK2-specific inhibitors are more efficacious than dual JAK1/2 inhibitors against JAK2-amplified TNBCs. Furthermore, JAK2 amplification is a potential biomarker for JAK2-dependence which, in turn, can be used to select patients for clinical trials with JAK2 inhibitors.

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Section: Introductionmentioning

confidence: 99%

Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence

et al. 2016

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“…Phosphatizing the tyrosine residues of ITIMs can recruit the effectors of Src homology phosphotyrosine phosphatase-1 (SHP-1) and SHP-2, and send an intracellular signal. SHP-1 has been reported to be a negative regulator of angiogenesis (21), and is overexpressed in breast cancer (22). In addition, upregulation of SHP-2 has been found in gastric cancer (23) and HCC (24,25).…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer

Wang

Zhang

Miao

et al. 2016

Experimental and Therapeutic Medicine

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Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is broadly expressed on the majority of immune cells; however, the biological role of LAIR in solid tumors has yet to be elucidated. In the present study, using immunohistochemical staining analysis, the expression of LAIR-1 in human cervical cancer (HCC) and nontumor-adjacent tissue specimens was determined, and the results indicated that the expression of LAIR-1 in HCC tissue was higher compared with that in noncancerous tissue. The χ2 test was used to analyze the correlation between the expression of LAIR-1 in tumor tissues with clinicopathological parameters. The results showed that the expression of LAIR-1 in the cancer cell nucleus was significantly associated with tumor size, pathological differentiation, T classification and clinical stage. In addition, the expression in the cytoplasm was evidently associated with the number of positive lymph nodes. The HCC cell line, ME-180, which does not express LAIR-1, was stably transfected using LAIR-1 cDNA. Cell Counting Kit-8 and an annexin V assay showed that the overexpression of LAIR-1 in ME-180 cells suppressed the proliferation and anti-apoptosis capacity of the cells. These findings demonstrated that LAIR-1 is markedly overexpressed in HCC tissue, and that its expression status is associated with tumor progression. LAIR-1 may be a biomarker and target in the diagnosis and treatment of patients with HCC.

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“…Activated SHP-1 has been demonstrated to catalyze tyrosine dephosphorylation of the Janus kinases (JAKs), src and c-fms, leading to the reduction or loss of kinase activity and the inhibition of cell proliferation (14,16–19,22–26). SHP-1 has been reported to be a negative regulator of angiogenesis (27) and to be upregulated in breast cancer (28). Although SHP-1 was demonstrated to be a negative regulator of proliferation, knockdown of SHP-1 resulted in CDK6 downregulation and G1/S cell cycle arrest in prostate cancer cells (20,29).…”

Section: Introductionmentioning

confidence: 99%

Alterations of cell cycle control proteins SHP-1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells

Peng

Cao

et al. 2014

Molecular Medicine Reports

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The primary treatment for nasopharyngeal carcinoma (NPC) is radiotherapy, with or without concurrent chemotherapy. However, resistance to radiotherapy is not uncommon. The aim of the present study was to establish a radioresistant NPC cell line to study the molecular mechanisms of radioresistance by measuring the expression of cell cycle control proteins src homology 2 domain-containing phosphatase (SHP)-1/2, p16, CDK4 and cyclin D1. Human nasopharyngeal carcinoma CNE-2 cells were cultured, divided into two groups (CNE-2S1 and CNE-2S2) and irradiated with a dose of 6 Gy x5 or 2 Gy x15, respectively. The cells were subcultured between doses of irradiation. The surviving sublines (CNE-2S1 and CNE-2S2 clones) were then passaged for three months and their radiosensitivity was determined. The cell cycle distribution and protein expression of SHP-1/2, p16, CDK4 and cyclin D1 in parental and progenitor cell lines were measured. Small interfering (si)RNA-mediated knockdown of SHP-1 and SHP-2 in the NPC cells was used to further examine their roles in radiosensitivity and cell cycle distribution. CNE-2S1, a radio-resistant cell line, had a significantly higher percentage of cells in S phase and a lower percentage of cells in G1 phase, enhanced expression levels of SHP-1, CDK4 and cyclin D1, and reduced expression of p16, respectively, as compared with the parent cells. Stable suppression of SHP-1 mRNA in CNE-2 cells resulted in increased radiosensitivity compared with the parental cells, a decrease in the number of cells in S phase and an increase in the expression of p16. The results suggested that the SHP-1/p16/cyclin D1/CDK4 pathway may have a role in regulating radiosensitivity and cell cycle distribution in nasopharyngeal cells.

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Up-regulation of the protein tyrosine phosphatase SHP-1 in human breast cancer and correlation withGRB2 expression

Cited by 59 publications

References 36 publications

Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence

Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence

Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer

Alterations of cell cycle control proteins SHP-1/2, p16, CDK4 and cyclin D1 in radioresistant nasopharyngeal carcinoma cells

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