H. pylori CagA activates the NLRP3 inflammasome to promote gastric cancer cell migration and invasion

Zhang, Xiaoyi; Li, Chao; Chen, Dingyu; He, Xingxing; Zhao, Yan; Bao, LiYa; Wang, Qingrong; Zhou, Jianjiang; Xie, Yuan

doi:10.1007/s00011-021-01522-6

Cited by 44 publications

(31 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the cytotoxin-related gene A (CagA) protein, an important pathogenic factor of Helicobacter pylori ( H. pylori ) [ 143 ], promotes the invasion and migration of GC cells by activating NLRP3 inflammasome, while the suppression of H. pylori -triggered inflammatory response and the depression of pyroptosis via the ROS/NLRP3/caspase-1/IL-1 β pathway may suppress the progression of GC [ 144 ]. These results indicate that there is a close and complex relationship between GC and pyroptosis, while more researches are necessary in future.…”

Section: Pyroptosis and Cancermentioning

confidence: 99%

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Qian

Bai

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

As a type of regulated cell death (RCD) mode, pyroptosis plays an important role in several kinds of cancers. Pyroptosis is induced by different stimuli, whose pathways are divided into the canonical pathway and the noncanonical pathway depending on the formation of the inflammasomes. The canonical pathway is triggered by the assembly of inflammasomes, and the activation of caspase-1 and then the cleavage of effector protein gasdermin D (GSDMD) are promoted. While in the noncanonical pathway, the caspase-4/5/11 (caspase 4/5 in humans and caspase 11 in mice) directly cleave GSDMD without the assembly of inflammasomes. Pyroptosis is involved in various cancers, such as lung cancer, gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma. Pyroptosis in gastric cancer, hepatic carcinoma, breast cancer, and colorectal carcinoma is related to the canonical pathway, while both the canonical and noncanonical pathway participate in lung cancer. Moreover, simvastatin, metformin, and curcumin have effect on these cancers and simultaneously promote the pyroptosis of cancer cells. Accordingly, pyroptosis may be an important therapeutic target for cancer.

show abstract

Section: Pyroptosis and Cancermentioning

confidence: 99%

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Qian

Bai

et al. 2022

Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…The authors reported that CagA also participates in the generation of intracellular ROS and that ROS inhibition has the potential to disrupt the NLRP3 pathway and pyroptosis. With these findings, the authors concluded that NLRP3 plays a key role in the action of CagA on gastric cells and that silencing NLRP3 can limit the effects of migration and invasion of cancer cells caused by CagA[ 99 ].…”

Section: Role Of Caga In Gastric Carcinogenesismentioning

confidence: 99%

Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis

Melo¹,

Marques²,

Pinheiro³

et al. 2022

World J Clin Oncol

View full text Add to dashboard Cite

Gastric cancer is the fifth most common malignancy and third leading cancer-related cause of death worldwide. Helicobacter pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3% of the world’s population and represents the main risk factor for the onset of gastric neoplasms. CagA is the most important virulence factor in H. pylori , and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous lesions. Upon translocation and tyrosine phosphorylation, CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways, thereby disrupting cell proliferation, differentiation and apoptosis. All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes. In this sense, once gastric cancer sets in, its perpetuation is independent of the presence of the oncoprotein, characterizing a “hit-and-run” carcinogenic mechanism. Therefore, this review aims to describe H. pylori - and CagA-related oncogenic mechanisms, to update readers and discuss the novelties and perspectives in this field.

show abstract

“…Also found that low expression or inhibited expression of gasdermin D (GSDMD) can promote tumour cell proliferation in GC. Zhang X et al ( Zhang et al, 2021 ). Showed that the H. pylori cytotoxin-related gene A (CagA) protein can activate the NOD-like receptor protein 3 (NLRP3) inflammasome pyroptosis pathway and promote GC cell migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer

Cao

Hu²,

Yuan

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

As a new programmed death mode, pyroptosis plays an indispensable role in gastric cancer (GC) and has strong immunotherapy potential, but the specific pathogenic mechanism and antitumor function remain unclear. We comprehensively analysed the overall changes of pyroptosis-related genes (PRGs) at the genomic and epigenetic levels in 886 GC patients. We identified two molecular subtypes by consensus unsupervised clustering analysis. Then, we calculated the risk score and constructed the risk model for predicting prognostic and selected nine PRGs related genes (IL18RAP, CTLA4, SLC2A3, IL1A, KRT7,PEG10, IGFBP2, GPA33, and DES) through LASSO and COX regression analyses in the training cohorts and were verified in the test cohorts. Consequently, a highly accurate nomogram for improving the clinical applicability of the risk score was constructed. Besides, we found that multi-layer PRGs alterations were correlated with patient clinicopathological features, prognosis, immune infiltration and TME characteristics. The low risk group mainly characterized by increased microsatellite hyperinstability, tumour mutational burden and immune infiltration. The group had lower stromal cell content, higher immune cell content and lower tumour purity. Moreover, risk score was positively correlated with T regulatory cells, M1 and M2 macrophages. In addition, the risk score was significantly associated with the cancer stem cell index and chemotherapeutic drug sensitivity. This study revealed the genomic, transcriptional and TME multiomics features of PRGs and deeply explored the potential role of pyroptosis in the TME, clinicopathological features and prognosis in GC. This study provides a new immune strategy and prediction model for clinical treatment and prognosis evaluation.

show abstract

H. pylori CagA activates the NLRP3 inflammasome to promote gastric cancer cell migration and invasion

Cited by 44 publications

References 34 publications

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Targeted Pyroptosis Is a Potential Therapeutic Strategy for Cancer

Influence of Helicobacter pylori oncoprotein CagA in gastric cancer: A critical-reflective analysis

Identification of pyroptosis-related subtypes, development of a prognostic model, and characterization of tumour microenvironment infiltration in gastric cancer

Contact Info

Product

Resources

About