Causes and consequences of microsatellite instability in gastric carcinogenesis

Velho, Sérgia; Fernandes, Maria Sofia; Leite, Marina Concli; Figueiredo, Céu; Seruca, Raquel

doi:10.3748/wjg.v20.i44.16433

Cited by 68 publications

(68 citation statements)

References 124 publications

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“…MSI is a common feature of gastric cancers that occurs in 15-30% of cases (5). DNA mismatch repair deficiency such as methylation of the MLH1 promoter increases the frequency of mutations across the genome, creating MSI (5). Not only MLH1 but also many other tumor suppressor genes are frequently hypermethylated in MSI-positive gastric cancer (6).…”

Section: Introductionmentioning

confidence: 99%

“…Nearly 9% of gastric cancer is EBV-positive (3), for which methylation of tumor suppressor genes is a key abnormality (4). MSI is a common feature of gastric cancers that occurs in 15-30% of cases (5). DNA mismatch repair deficiency such as methylation of the MLH1 promoter increases the frequency of mutations across the genome, creating MSI (5).…”

Section: Introductionmentioning

confidence: 99%

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Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Kim

Baek

et al. 2016

International Journal of Oncology

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Abstract. SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR-218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Kim

Baek

et al. 2016

International Journal of Oncology

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“…The majority of epithelial cancers first spread through the lymph vessels into the draining LNs and gain metastatic development (3). The detection of metastasis in the sentinel LNs is often associated with adjuvant therapy decisions and has major prognostic implications for patients (4,5).…”

Section: Introductionmentioning

confidence: 99%

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

Zhu

Hu²,

Wei

et al. 2018

Oncol Lett

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Abstract. Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC. Therefore, the molecular mechanisms of LN metastasis in GC development require further investigation. Recently, a large number of clinical studies have focused on the molecular mechanisms and biological markers of tumor invasion and metastasis. However, few articles have broadly summarized LN metastasis in GC, and the molecular mechanisms of LN metastasis are not yet fully understood. In the present review, the molecular mechanisms of LN metastasis in GC will be discussed, including the following aspects: Cell adhesion and movement, ECM degradation, new vessel formation, and molecular pattern differences between metastatic LNs and the primary tumor. This review may lead to a better understanding of LN metastasis in GC, and the identification of new diagnostic markers.

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“…Due to lack of main clinical manifestations, gastric cancer patients usually developed the advanced lymph node metastasis [2], which accounts for the high mortality of patients with gastric cancer [3,4]. However, the detailed mechanisms underlying gastric cancer cell motility, invasiveness, or metastasis have not been thoroughly figured out.…”

Section: Introductionmentioning

confidence: 98%

C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer

2015

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In our previous study, the epithelial-to-mesenchymal transition (EMT) has been identified to be involved in gastric cancer progression. Notably, nuclear protein C23 and bone morphogenetic protein-2 (BMP2) have been linked into EMT. However, the specific mechanisms underlying BMP2 pathway-mediated EMT are not still unraveled. In this study, we adopted immunohistochemistry and immunoblotting to determine the expression of C23 and BMP2 receptor II (BMPR-II) in 90 gastric cancer samples and cell lines. Subsequently, relevant cell lines were selected to be treated with si-C23 or si-BMPRII and the detection of in vitro assay. Our results revealed that both C23 and BMPRII were aberrantly and constitutively expressed in gastric cancer specimens and cell lines, whose expression was positively associated with metastasis, stage and differentiation, and portended poor survival outcome of gastric cancer patients. In vitro assay validated the increased expression of p-Erk1/2, p-Akt, vimentin, N-cadherin, and MMP2 in BMP2-stimulated MGC803 cells, which was in a dose-dependent manner. By contrast, si-C23 treatment attenuated the BMP2-stimulated expression of p-Erk1/2, p-Akt, vimentin, N-cadherin, and MMP2. Also, the treatment of either si-C23 or si-BMPRII decreased the ability of migration and invasion of MGC803 cells. In conclusion, C23 mediates BMP2-induced EMT progression via the up-regulation of Erk1/2 and Akt signaling pathway in gastric cancer, which indicated both C23 and BMPRII pathway could be recommended as prospective targets or biomarkers to antagonize the progression of gastric cancer.

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Causes and consequences of microsatellite instability in gastric carcinogenesis

Cited by 68 publications

References 124 publications

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

C23 protein meditates bone morphogenetic protein-2-mediated EMT via up-regulation of Erk1/2 and Akt in gastric cancer

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