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 Long-Term Helicobacter pylori Infection Switches Gastric Epithelium Reprogramming towards Cancer Stem Cell-Related Differentiation Program in Hp-Activated Gastric Fibroblast-TGFβ Dependent Manner

2020 ◽  
Vol 8 (10) ◽  
pp. 1519
Author(s):  
Gracjana Krzysiek-Maczka ◽  
Aneta Targosz ◽  
Urszula Szczyrk ◽  
Tomasz Wrobel ◽  
Malgorzata Strzalka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Epithelium ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Cancer Associated Fibroblast ◽  
Activated Fibroblasts

Helicobacter pylori (Hp)-induced inflammatory reaction leads to a persistent disturbance of gastric mucosa and chronic gastritis evidenced by deregulation of tissue self-renewal and local fibrosis with the crucial role of epithelial–mesenchymal transition (EMT) in this process. As we reported before, Hp activated gastric fibroblasts into cells possessing cancer-associated fibroblast properties (CAFs), which secreted factors responsible for EMT process initiation in normal gastric epithelial RGM1 cells. Here, we showed that the long-term incubation of RGM1 cells in the presence of Hp-activated gastric fibroblast (Hp-AGF) secretome induced their shift towards plastic LGR5+/Oct4high/Sox-2high/c-Mychigh/Klf4low phenotype (l.t.EMT+RGM1 cells), while Hp-non-infected gastric fibroblast (GF) secretome prompted a permanent epithelial–myofibroblast transition (EMyoT) of RGM1 cells favoring LGR−/Oct4high/Sox2low/c-Myclow/Klf4high phenotype (l.t.EMT−RGM1 cells). TGFβ1 rich secretome from Hp-reprogrammed fibroblasts prompted phenotypic plasticity and EMT of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGFβR1 and TGFβR2 activity. In turn, TGFβR1 activity along with GF-induced TGFβR2 activation in l.t.EMT−RGM1 cells prompted their stromal phenotype. Collectively, our data show that infected and non-infected gastric fibroblast secretome induces alternative differentiation programs in gastric epithelium at least partially dependent on TGFβ signaling. Hp infection-activated fibroblasts can switch gastric epithelium microevolution towards cancer stem cell-related differentiation program that can potentially initiate gastric neoplasm.

scholarly journals Helicobacter pylori generates cells with cancer stem cell properties via epithelial–mesenchymal transition-like changes

Oncogene ◽  
2013 ◽  
Vol 33 (32) ◽  
pp. 4123-4131 ◽  
Author(s):  
E Bessède ◽  
C Staedel ◽  
L A Acuña Amador ◽  
P H Nguyen ◽  
L Chambonnier ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

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 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.

Roles of Helicobacter pylori in the Epithelial-Mesenchymal Transition of Gastric Cancer

2020 ◽  
Vol 04 (04) ◽  
Author(s):  
Shuai Ruan ◽  
Wenjie Huang ◽  
Fang Wen ◽  
Xiaona Lu ◽  
Su Ping Gu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

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