scholarly journals MicroRNAs Associated with Epithelial-Mesenchymal Transition Can Be Targeted to Inhibit Peritoneal Dissemination of Human Scirrhous Gastric Cancers

Pathobiology ◽  
2018 ◽  
Vol 85 (4) ◽  
pp. 232-246 ◽  
Author(s):  
Yoshifumi Takei ◽  
Guodong Shen ◽  
Ayami Morita-Kondo ◽  
Toshifumi Hara ◽  
Keichiro Mihara ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Mesenchymal Transition ◽  
Gastric Cancers

scholarly journals Long Noncoding RNA HOTAIR Promotes Epithelial-Mesenchymal Transition and Is a Suitable Target to Inhibit Peritoneal Dissemination in Human Scirrhous Gastric Cancers

Pathobiology ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 277-290
Author(s):  
Yoshifumi Takei ◽  
Toshifumi Hara ◽  
Akiko Suzuki ◽  
Keichiro Mihara ◽  
Kazuyoshi Yanagihara
Keyword(s):  
Gastric Cancer ◽  
Cell Line ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Peritoneal Dissemination ◽  
Luciferase Assay ◽  
Scirrhous Gastric Cancer ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Original Cell

<b><i>Objectives:</i></b> Scirrhous gastric cancer, which accounts for approximately 10% of all gastric cancers, often disseminates to the peritoneum, leading to intractable cases with poor prognosis. There is an urgent need for new treatment approaches for this difficult cancer. <b><i>Methods:</i></b> We previously established an original cell line, HSC-60, from a scirrhous gastric cancer patient and isolated a peritoneal-metastatic cell line, 60As6, in nude mice following orthotopic inoculations. In the present study, we focused on the expression of long noncoding ribonucleic acid (RNA) (lncRNA) in the cell lines and investigated the mechanism on peritoneal dissemination. <b><i>Results:</i></b> We demonstrated that an lncRNA, HOX transcript antisense RNA (HOTAIR), is expressed significantly more highly in 60As6 than HSC-60 cells. Then, using both HOTAIR knockdown and overexpression experiments, we showed that high-level expression of HOTAIR promotes epithelial-mesenchymal transition (EMT) in 60As6 cells. By luciferase assay, we found that HOTAIR directly targets and binds to miR-217, and that miR-217 directly binds to Zinc finger E-box-binding homeobox 1 (ZEB1). The knockdown of HOTAIR in 60As6 cells significantly reduced the invasion activity and peritoneal dissemination – and significantly prolonged the survival – in the orthotopic tumor mouse model. <b><i>Conclusion:</i></b> An EMT-associated pathway (the HOTAIR-miR-217-ZEB1 axis) appears to inhibit peritoneal dissemination and could lead to a novel therapeutic strategy against scirrhous gastric cancer in humans.

scholarly journals Novel Gastric Cancer Stem Cell-Related Marker LINGO2 Is Associated with Cancer Cell Phenotype and Patient Outcome

2019 ◽  
Vol 20 (3) ◽  
pp. 555 ◽  
Author(s):  
Jung Jo ◽  
Soo Park ◽  
Semi Park ◽  
Hee Lee ◽  
Chanyang Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Motility ◽  
Epithelial Mesenchymal Transition ◽  
Cell Phenotype ◽  
Interacting Protein ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Extracellular Signal ◽  
Gastric Cancer Treatment

The expression of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) has been reported in Parkinson’s disease; however, its role in other diseases is unknown. Gastric cancer is the second leading cause of cancer death. Cancer stem cells (CSC) are a subpopulation of cancer cells that contribute to the initiation and invasion of cancer. We identified LINGO2 as a CSC-associated protein in gastric cancers both in vitro and in patient-derived tissues. We studied the effect of LINGO2 on cell motility, stemness, tumorigenicity, and angiogenic capacity using cells sorted based on LINGO2 expression and LINGO2-silenced cells. Tissue microarray analysis showed that LINGO2 expression was significantly elevated in advanced gastric cancers. The overall survival of patients expressing high LINGO2 was significantly shorter than that of patients with low LINGO2. Cells expressing high LINGO2 showed elevated cell motility, angiogenic capacity, and tumorigenicity, while LINGO2 silencing reversed these properties. Silencing LINGO2 reduced kinase B (AKT)/extracellular signal-regulated kinase (ERK)/ERK kinase (MEK) phosphorylation and decreased epithelial-mesenchymal transition (EMT)-associated markers—N-Cadherin and Vimentin and stemness-associated markers— POU class 5 homeobox 1 (OCT4) and Indian hedgehog (IHH), and markedly decreased the CD44+ population. These indicate the involvement of LINGO2 in gastric cancer initiation and progression by altering cell motility, stemness, and tumorigenicity, suggesting LINGO2 as a putative target for gastric cancer treatment.

scholarly journals Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial-Mesenchymal Transition in Breast, Lung and Gastric Cancers

2018 ◽  
Vol 19 (8) ◽  
pp. 2411 ◽  
Author(s):  
Armando Cevenini ◽  
Stefania Orrù ◽  
Annamaria Mancini ◽  
Andreina Alfieri ◽  
Pasqualina Buono ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Signatures ◽  
Insulin Like Growth Factor ◽  
Cancer Proliferation ◽  
Igf Binding Proteins ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Igf System ◽  
Igf Binding

The insulin-like growth factor (IGF) system, which is constituted by the IGF-1 and IGF-2 peptide hormones, their corresponding receptors and several IGF binding proteins, is involved in physiological and pathophysiological processes. The IGF system promotes cancer proliferation/survival and its signaling induces the epithelial-mesenchymal transition (EMT) phenotype, which contributes to the migration, invasiveness, and metastasis of epithelial tumors. These cancers share two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK. However, as far as we could review at this time, each type of cancer cell undergoes EMT through tumor-specific routes. Here, we review the tumor-specific molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.

Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial–mesenchymal transition in gastric cancers

2011 ◽  
Vol 137 (11) ◽  
pp. 1697-1704 ◽  
Author(s):  
Jung Hwan Yoon ◽  
Young Hwi Kang ◽  
Yoo Jin Choi ◽  
In Soo Park ◽  
Suk Woo Nam ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Gastric Cancers ◽  
Gastrokine 1
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