Clinical significance of MET in gastric cancer

Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

doi:10.4251/wjgo.v7.i11.317

Cited by 35 publications

(27 citation statements)

References 76 publications

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“…Moreover, FGFR2 amplification was mutually exclusive from the amplification of other RTKs [4]. The overexpression of HER2 or c-MET was observed more frequently in IGC than in DGC [6, 24], suggesting that a signaling pathway activated by these RTKs might have a critical role in the progression and prognosis of IGC. HER2 overexpression was often found in IGC without significant association of FGFRs in this study, and our results might support those of another study reporting exclusive RTK expression [5].…”

Section: Discussionmentioning

confidence: 99%

Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer

et al. 2017

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BackgroundReceptor tyrosine kinases promote tumor progression in many cancers, although oncologic activation differs between diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC). Fibroblast growth factor receptor (FGFR) is one RTK, and we previously reported the clinical significance of FGFR1, 2, 3, and 4 in gastric cancer. The aim of the present study was to reevaluate the clinical significance of FGFR1–4 expression separately in DGC and IGC.MethodsTumor samples, including 109 DGCs and 100 IGCs, were obtained from patients who underwent gastrectomy between 2003 and 2007 in our institution. The expression levels of FGFR1, 2, 3, and 4 were measured in the tumors by immunohistochemical analysis.ResultsIn DGC, high expression of FGFR1, FGFR2, or FGFR4 was significantly associated with the depth of invasion, lymph-node metastasis, pathological stage, and distant metastasis or recurrent disease. Patients with high expression of FGFR1, FGFR2, or FGFR4 had significantly poorer disease-specific survival (DSS) (p = 0.009, p = 0.001, and p = 0.023, respectively). In IGC, only FGFR4 expression was significantly associated with factors relative to tumor progression and with shorter DSS (p = 0.012).ConclusionIn conclusion, high FGFR4 expression correlated with tumor progression and survival in both DGC and IGC, whereas high expression of FGFR1 and 2 correlated with tumor progression and survival in only DGC.

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Section: Discussionmentioning

confidence: 99%

Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer

et al. 2017

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“…As for the two other gastric cancer cell strains, N87 and SGC7901 cells had elevated ANGPTL2 protein expression levels that were slightly lower compared to normal levels. The probable explanation is that the N87 and SGC7901 cell lines had a lower metastatic capacity and the BGC823 and PAMC82 cell lines had a higher degree of malignancy, which exhibited strong migratory ability[32-34]. Recent studies have reported that the carcinogenic capacity of PAMC82 cells is higher than that of N87 cells[35,36].…”

Section: Discussionmentioning

confidence: 99%

ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

Sheng¹,

Chen²,

Tu³

et al. 2016

WJG

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AIMTo explore expression of angiopoietin-like protein 2 (ANGPTL2) and its effect on biological behavior such as proliferation and invasiveness in gastric cancer.METHODSWestern blotting was used to detect expression of ANGPTL2 in 60 human normal gastric tissues, 60 human gastric cancer tissues and gastric cell lines including GES-1, N87, SGC7901, BGC823 and PAMC82. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assay were used to detect the proliferation and invasive ability of gastric cancer cells.RESULTSCompared to normal tissues, ANGPTL2 protein levels were significantly upregulated in gastric tissues, and this level was closely correlated with gastric tumor grade, clinical stage and lymph node metastasis. Compared to GES-1 cells, ANGPTL2 mRNA and protein levels were significantly increased in gastric cancer cells including N87, SGC7901, BGC823 and PAMC82. The expression of ANGPTL2 in highly malignant gastric cancer cell lines BGC823 and PAMC82 was significantly higher than in low malignancy gastric cancer cell lines N87 and SGC7901. MTT and Transwell experiments indicated that the proliferation rate and invasive ability of stable overexpressed gastric cancer cells was faster than in cells transfected with Lv-NC and blank control cells, and the invasive ability of stable overexpressed gastric cancer cells was higher than that of cells transfected with Lv-NC and blank control cells.CONCLUSIONANGPTL2 contributed to proliferation and invasion of gastric cancer cells. In clinical treatment, ANGPTL2 may become a new target for treatment of gastric cancer.

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“…As another important member of RTK family, c-Met has similar molecular structure and is overexpressed in gastric cancer cells [37, 38]. Therefore, we hypothesized that PKG II may exert a similar inhibitory on the activation of c-Met.…”

Section: Discussionmentioning

confidence: 99%

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

Yao²,

Zhu

et al. 2016

Oncotarget

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Previous studies showed that type II cGMP-dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR). Both c-Met and EGFR belong to family of receptor tyrosine kinases (RTKs) and have high molecular analogy. However, the effect of PKG II on c-Met activation is unclear. This study was designed to investigate the inhibitory effect of PKG II on the activation of c-Met and consequent biological activities. The results from CCK8 assay, Transwell assay and TUNEL assay showed that HGF enhanced cell proliferation and migration, and decreased cell apoptosis. Activated PKG II reversed the above changes caused by HGF. Immunoprecipitation and Western blotting results showed that PKG II could bind with c-Met and phosphorylate its Ser985, and thereby inhibited HGF-induced activation of c-Met and MAPK/ERK and PI3K/Akt/mTOR mediated signal transduction. When Ser985 of c-Met was mutated to Alanine for preventing phosphorylation of this site, the blocking effect of PKG II on c-Met activation was annulled. When Ser985 of c-Met was mutated to Aspartic acid for mimicking phosphorylation of this site, HGF-induced activation of c-Met was prevented. In conclusion, the results indicated that PKG II could block c-Met activation via phosphorylating Ser985 of this RTK.

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Clinical significance of MET in gastric cancer

Cited by 35 publications

References 76 publications

Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer

Different clinical significance of FGFR1–4 expression between diffuse-type and intestinal-type gastric cancer

ANGPTL2 expression in gastric cancer tissues and cells and its biological behavior

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

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