Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

Shin, Namsoo; Jeong, Eun; Choi, Chang In; Moon, Hyun Jung; Kwon, Chae Hwa; Chu, In Sun; Kim, Gwang Ha; Jeon, Tae Yong; Kim, Dae Hwan; Lee, Jae Hyuk; Park, Do Youn

doi:10.1186/1471-2407-12-521

Cited by 85 publications

(76 citation statements)

References 29 publications

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“…2A and B). The zinc finger-containing proteins Snail and Slug and the helix-loop-helix transcription factor Twist repress E-cadherin expression and induce EMT in gastric cancer [24-26]. We thus assessed the expression levels of the above E-cadherin regulators in RhoGDI2-overexpressing SNU-484 cells to determine the effect of RhoGDI2.…”

Section: Resultsmentioning

confidence: 99%

RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells

et al. 2014

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Rho GDP dissociation inhibitor 2 (RhoGDI2) expression correlates with tumor growth, metastasis, and chemoresistance in gastric cancer. Here, we show that RhoGDI2 functions in the epithelial-mesenchymal transition (EMT), which is responsible for invasiveness during tumor progression. This tumorigenic activity is associated with repression of E-cadherin by RhoGDI2 via upregulation of Snail. Overexpression of RhoGDI2 induced phenotypic changes consistent with EMT in gastric cancer cells, including abnormal epithelial cell morphology, fibroblast-like properties, and reduced intercellular adhesion. RhoGDI2 overexpression also resulted in decreased expression of the epithelial markers E-cadherin and β-catenin and increased expression of the mesenchymal markers vimentin and fibronectin. Importantly, RhoGDI2 overexpression also stimulated the expression of Snail, a repressor of E-cadherin and inducer of EMT, but not other family members such as Slug or Twist. RNA interference-mediated knockdown of Snail expression suppressed RhoGDI2-induced EMT and invasion, confirming that the effect was Snail-specific. These results indicate that RhoGDI2 plays a critical role in tumor progression in gastric cancer through induction of EMT. Targeting RhoGDI2 may thus be a useful strategy to inhibit gastric cancer cell invasion and metastasis.

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Section: Resultsmentioning

confidence: 99%

RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells

et al. 2014

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“…Besides, the involvement of NF-κB-Snail-E-cadherin axis or CCR7 pathway in induction of EMT through upregulating Snail signaling proved in GC both implied the decisive role of Snail explicitly (25,26). Furthermore, Shin et al (27) reported that Snail could be a prognostic predictor of gastric cancer due to its strong interrelationship with tumor progression, lymph node metastasis, lymphovascular or perineural invasion. Twist protein is a member of the basic/helix-loop-helix transcription factor family and binds selectively to the E-box consensus sequence to regulate target genes such as E-cadherin (28).…”

Section: Epithelial-mesenchymal Transition and Gastric Cancermentioning

confidence: 99%

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

Zhuang

Jiang

et al. 2016

International Journal of Oncology

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Abstract. Gastric cancer (GC) is the third primary cause of cancer-related mortality and one of the most common type of malignant diseases worldwide. Despite remarkable progress in multimodality therapy, advanced GC with high aggressiveness always ends in treatment failure. Epithelialmesenchymal transition (EMT) has been widely recognized to be a key process associating with GC evolution, during which cancer cells go through phenotypic variations and acquire the capability of migration and invasion. Wnt/β-catenin pathway has established itself as an EMT regulative signaling due to its maintenance of epithelial integrity as well as tight adherens junctions while mutations of its components will lead to GC initiation and diffusion. The E-cadherin/β-catenin complex plays an important role in stabilizing β-catenin at cell membrane while disruption of this compound gives rise to nuclear translocation of β-catenin, which accounts for upregulation of EMT biomarkers and unfavorable prognosis. Additionally, several microRNAs positively or negatively modify EMT by reciprocally acting with certain target genes of Wnt/β-catenin pathway in GC. Thus, this review centers on the strong associations between Wnt/β-catenin pathway and microRNAs during alteration of EMT in GC, which may induce advantageous therapeutic strategies for human gastric cancer.

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“…12 Intriguingly, increased Snail expression is detected in metastatic gastric-cancer cells and is required for EMT and gastric-cancer cells migration and invasion. 13 WAVE3, a member of the WASP (Wiskott-Aldrich syndrome protein)/WAVE actin cytoskeleton remodeling family of proteins, is critical for the motility, migration and invasive properties of cancer cells. 14 More importantly, Taylor et al 15 reported in 2013 that WAVE3 expression is required in mediating the initiation of EMT programs stimulated by TGF-β.…”

Section: Introductionmentioning

confidence: 99%

WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

et al. 2014

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WAVE3, an actin cytoskeleton remodeling protein overexpressed in many kinds of cancers, has been associated with a lot of metastatic diseases. However, the role and mechanisms of the high expression of WAVE3 in human gastric cancer has not been fully elucidated. Here we demonstrated that WAVE3 was expressed in all six kinds of gastric-cancer cell lines: BGC-823, SGC-7901, AGS, MGC803, MKN28 and MKN45. Furthermore, a correlation was found between aggressiveness of these cell lines and expression of WAVE3. Next, we investigated the role of WAVE3 in SGC-7901 cells and found that upregulating WAVE3 could promote the migration, invasion and proliferation of SGC-7901 cells in vitro. It has been reported that WAVE3 could induce cancer invasion and metastasis by participating epithelial-mesenchymal transition (EMT). However, the mechanisms are not entirely clear. In this study we showed that elevated WAVE3 levels could induce EMT in SGC-7901 cells by dampening the expression of E-cadherin while increasing the expression of vimentin. Elevated WAVE3 levels could also improve the expression of transcription factor Snail. In addition, downregulating Snail could particularly reduce EMT and the metastasis, invasion and proliferation activity in SGC-7901 cells elevated by overexpression of WAVE3. Taken together, we demonstrated that WAVE3 promoted gastric-cancer-cells migration and invasion by taking part in EMT via upregulation of Snail. WAVE3 could be a useful target for gastric-cancer prevention and therapy.

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Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

Cited by 85 publications

References 29 publications

RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells

RhoGDI2 promotes epithelial-mesenchymal transition via induction of Snail in gastric cancer cells

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

WAVE3 promotes epithelial–mesenchymal transition of gastric cancer through upregulation of Snail

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