Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis

Sigal, Michael; Logan, Cheryl A.; Kapałczyńska, Marta; Mollenkopf, Hans-Joachim; Berger, Hilmar; Wiedenmann, Bertram; Nusse, Roeland; Amieva, Manuel R.; Meyer, Thomas F.

doi:10.1038/nature23642

Cited by 169 publications

(198 citation statements)

References 27 publications

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“…It is reasonable to think that, similar to autocrine Rspo3, paracrine Rspo3 may also be involved in the activation of the Wnt/β‐catenin pathway and in the induction of cancer cell EMT and stemness. It has been shown that myofibroblast‐derived Rspo3 is required for the expression of Axin2 and Lgr5 in gastric epithelial stem cells . Moreover, both Wnt ligands and Rspo3 from platelet‐derived growth factor receptor alpha (PdgfRα)‐positive myofibroblasts are required to support the intestinal stem‐cell niche …”

Section: Wnt Signaling Is Involved In Epithelial‐stromal Crosstalk Ofmentioning

confidence: 99%

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

et al. 2018

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Wnt proteins, a group of secreted glycoproteins, mainly combine with receptors Frizzled (FZD) and/or low‐density‐lipoprotein receptor‐related proteins 5/6 (LRP5/6), initiating β‐catenin‐dependent and ‐independent signaling pathways. These pathways, which can be regulated by some secreted antagonists such as secreted Frizzled‐related proteins (SFRP) and dickkopf‐related protein (DKK), play a critical role in embryo development and adult homeostasis. Overactivation of Wnt signaling has been implicated in some human diseases including cancer. Wnt transgenic mice provide convincing evidence that Wnt signaling is involved in breast cancer initiation and progression, which is further strengthened by observations on human clinical breast cancer patients and studies on in vitro cultured human breast cancer cells. This review focuses on the roles of Wnt ligands, receptors and antagonists in breast cancer development instead of molecules or signaling transactivating β‐catenin independent on Wnt upstream components.

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Section: Wnt Signaling Is Involved In Epithelial‐stromal Crosstalk Ofmentioning

confidence: 99%

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

et al. 2018

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“…Other toxins, such as VacA and CagL, as well as Hp components, such as LPS, also contribute to this malignant transformation. Recently, a group reported that Hp can promote GC by activating gastric stem cells . The gastric carcinogenesis initiated by Hp can be partially attributed to changes in signaling pathways, and the most studied pathways are toll‐like receptor‐4 (TLR‐4) and nuclear factor‐κβ (NF‐κB) signaling …”

Section: Discussionmentioning

confidence: 99%

“…Recently, a group reported that Hp can promote GC by activating gastric stem cells. 32 The gastric carcinogenesis initiated by Hp can be partially attributed to changes in signaling pathways, and the most studied pathways are toll-like receptor-4 (TLR-4) and nuclear factor-κβ (NF-κB) signaling. 33,34 Activation of TLR-4 triggers a cascade of downstream signaling pathways, including phosphorylation of the mitogen-activated protein kinase (MAPK) pathway, which contains the components extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori‐induced YAP1 nuclear translocation promotes gastric carcinogenesis by enhancing IL‐1β expression

Shen

Liang

et al. 2019

Cancer Medicine

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Gastric cancer (GC) is one of the most common and malignant pathologies, and a significant portion of GC incidences develops from Helicobacter pylori (Hp) ‐induced chronic gastritis. Although the exact mechanisms of GC are complex and poorly understood, gastric carcinogenesis is a good model to investigate how inflammation and infection collaboratively promote tumorigenesis. Yes‐associated protein 1 (YAP1) is the key effector of the Hippo pathway, which is silenced in most human cancers. Herein, we verified the tumor‐promoting effect of YAP1 in vitro, in vivo, and in human specimens. We revealed that YAP1 displays nuclear translocation and works with TEAD to activate transcription of the crucial inflammatory cytokine IL‐1β in gastric cells infected with Hp . As IL‐1ß accounts for inflammation‐associated tumorigenesis, this process can lead to gastric carcinogenesis. Thus, in addition to activating proliferation genes, YAP1 also plays a major role in inflammation amplification by activating inflammatory cytokine genes. Excitingly, our research demonstrates that transfection of mutant plasmid YAP‐5SA/S94A or addition of the drug verteporfin, both of which are thought to disrupt the YAP1‐TEAD interaction, can arrest the carcinogenesis process. These findings can provide new approaches to GC treatment.

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“…In addition to local interactions, new research revealed the importance of longer‐range interactions to mediate gland hyperplasia which is a hallmark of H. pylori infection . Lineage tracing in the murine infection model revealed that H. pylori infection accelerates proliferation of an Axin2+ Lgr5‐ progenitor cell near the base of antral glands via induction of R‐spondin in underlying myofibroblasts.…”

Section: Helicobacter Pylori Gastric Colonizationmentioning

confidence: 99%

Pathogenesis of Helicobacter pylori infection

2018

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In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated structural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physiology were newly explored this year and evaluated for their functions during stomach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E-cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. pylori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technologies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new insights into how H. pylori manipulates gastric tissue functions, locally and at a distance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experimental infection after vaccination.

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Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis

Cited by 169 publications

References 27 publications

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

Wnt signaling in human and mouse breast cancer: Focusing on Wnt ligands, receptors and antagonists

Helicobacter pylori‐induced YAP1 nuclear translocation promotes gastric carcinogenesis by enhancing IL‐1β expression

Pathogenesis of Helicobacter pylori infection

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