scholarly journals Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

2020 ◽  
Vol 21 (7) ◽  
pp. 2544 ◽  
Author(s):  
Jacek Baj ◽  
Karolina Brzozowska ◽  
Alicja Forma ◽  
Amr Maani ◽  
Elżbieta Sitarz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Host Cell ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Carcinogenesis ◽  
World Health ◽  
Mesenchymal Transition ◽  
Methylation Of Dna ◽  
H Pylori

Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002–2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.

scholarly journals TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1462 ◽  
Author(s):  
Camille Tiffon ◽  
Julie Giraud ◽  
Silvia Elena Molina-Castro ◽  
Sara Peru ◽  
Lornella Seeneevassen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Carcinogenesis ◽  
Gastric Epithelium ◽  
Binding Motif ◽  
Mesenchymal Transition ◽  
H Pylori

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway effectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZ silencing reduced ZEB1 expression and EMT phenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.

scholarly journals Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1055 ◽  
Author(s):  
Jacek Baj ◽  
Izabela Korona-Głowniak ◽  
Alicja Forma ◽  
Amr Maani ◽  
Elżbieta Sitarz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Mesenchymal Transition ◽  
Treatment Strategies ◽  
Gastric Ulcers ◽  
Heparin Binding ◽  
Human Pathogens ◽  
Mesenchymal Transition ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world’s population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial–mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial–mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.

scholarly journals The Underappreciated Role of Epithelial Mesenchymal Transition in Chronic Obstructive Pulmonary Disease and Its Strong Link to Lung Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1394
Author(s):  
Malik Quasir Mahmood ◽  
Shakti D. Shukla ◽  
Chris Ward ◽  
Eugene Haydn Walters
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
World Health ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Mesenchymal Transition

The World Health Organisation reported COPD to be the third leading cause of death globally in 2019, and in 2020, the most common cause of cancer death was lung cancer; when these linked conditions are added together they come near the top of the leading causes of mortality. The cell-biological program termed epithelial-to-mesenchymal transition (EMT) plays an important role in organ development, fibrosis and cancer progression. Over the past decade there has emerged a substantial literature that also links EMT specifically to the pathophysiology of chronic obstructive pulmonary disease (COPD) as primarily an airway fibrosis disease; COPD is a recognised strong independent risk factor for the development of lung cancer, over and above the risks associated with smoking. In this review, our primary focus is to highlight these linkages and alert both the COPD and lung cancer fields to these complex interactions. We emphasise the need for inter-disciplinary attention and research focused on the likely crucial roles of EMT (and potential for its inhibition) with recognition of its strategic place mechanistically in both COPD and lung cancer. As part of this we discuss the future potential directions for novel therapeutic opportunities, including evidence-based strategic repurposing of currently used familiar/approved medications.

scholarly journals Epithelial to Mesenchymal Transition and Cell Biology of Molecular Regulation in Endometrial Carcinogenesis

2019 ◽  
Vol 8 (4) ◽  
pp. 439 ◽  
Author(s):  
Hsiao-Chen Chiu ◽  
Chia-Jung Li ◽  
Giou-Teng Yiang ◽  
Andy Tsai ◽  
Meng-Yu Wu
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Cell Biology ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Cell Metabolism ◽  
Basic Research ◽  
Genetic Mutation ◽  
Molecular Regulation ◽  
Mesenchymal Transition

Endometrial carcinogenesis is involved in several signaling pathways and it comprises multiple steps. The four major signaling pathways—PI3K/AKT, Ras/Raf/MEK/ERK, WNT/β-catenin, and vascular endothelial growth factor (VEGF)—are involved in tumor cell metabolism, growth, proliferation, survival, and angiogenesis. The genetic mutation and germline mitochondrial DNA mutations also impair cell proliferation, anti-apoptosis signaling, and epithelial–mesenchymal transition by several transcription factors, leading to endometrial carcinogenesis and distant metastasis. The PI3K/AKT pathway activates the ransforming growth factor beta (TGF-β)-mediated endothelial-to-mesenchymal transition (EMT) and it interacts with downstream signals to upregulate EMT-associated factors. Estrogen and progesterone signaling in EMT also play key roles in the prognosis of endometrial carcinogenesis. In this review article, we summarize the current clinical and basic research efforts regarding the detailed molecular regulation in endometrial carcinogenesis, especially in EMT, to provide novel targets for further anti-carcinogenesis treatment.

scholarly journals Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial–mesenchymal transition of gastric cancer cells

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chen Zeng ◽  
Ran Yan ◽  
Guanghua Yang ◽  
Sen Xiang ◽  
Fuli Zhao
Keyword(s):  
Gastric Cancer ◽  
Hedgehog Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Signaling Activation

Abstract Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.

Melittin suppresses epithelial–mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway

2021 ◽  
Author(s):  
Jye-Yu Huang ◽  
Shu-Fen Peng ◽  
Fu-Shin Chueh ◽  
Po-Yuan Chen ◽  
Yi-Ping Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

ABSTRACT Gastric cancer has a poor prognosis; once cancer has metastasized, it can easily lead to patient death. Melittin is one of the major components extracted from the bee venom. It has been shown that melittin emerges antitumor activities against many human cancer cell lines. Our results indicated that melittin at 0.2-0.5 µm significantly reduced total cell viability in human gastric cancer AGS cells. At low concentrations (0.05-0.15 µm), melittin displayed antimetastasis effects and inhibited cell adhesion and colony formation. Besides, it inhibited cell motility and suppressed cell migration and invasion. Melittin inhibited the activities of MMP-2 and MMP-9 and the integrity of cell membrane in AGS cells. Furthermore, Western blotting results showed that melittin decreased the protein expressions of Wnt/BMP and MMP-2 signaling pathways. Based on these observations, melittin inhibited cell migration and invasion of AGS cells through multiple signaling pathways. It may be used to treat metastasized gastric cancers in the future.

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