Increased Expression of Gremlin1 Promotes Proliferation and Epithelial Mesenchymal Transition in Gastric Cancer Cells and Correlates With Poor Prognosis of Patients With Gastric Cancer

Sun, Zhiwei; Cai, Sanjun; Liu, Chang; Cui, Yuxin; Ji, Jiafu; Jiang, Wen Guo; Ye, Lin

doi:10.21873/cgp.20167

Cited by 16 publications

(17 citation statements)

References 46 publications

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“…Not only are VEGF inhibitors directly responsible for downregulation of angiogenesis but the literature has suggested other compounds not specific to VEGF inhibition can downregulate angiogenesis. Bae et al suggested that metformin can inhibit the indirect feedback loop between CXCL8 and PTPRD (protein tyrosine phosphatase receptor delta) [119]. PTPRD downregulation is seen in gastric cancer leading to poorer overall survivals, while this axis has been shown to promote angiogenesis [119].…”

Section: Cancer-associated Fibroblasts and Angiogenesismentioning

confidence: 99%

“…Bae et al suggested that metformin can inhibit the indirect feedback loop between CXCL8 and PTPRD (protein tyrosine phosphatase receptor delta) [119]. PTPRD downregulation is seen in gastric cancer leading to poorer overall survivals, while this axis has been shown to promote angiogenesis [119]. A new compound, 5,6,7-trimethoxy flavonoid salicylate derivatives, was found to potently inhibit not only VEGF but also HIFa and may be effective in altering the angiogenic and hypoxic conditions of the tumor microenvironment [120].…”

Section: Cancer-associated Fibroblasts and Angiogenesismentioning

confidence: 99%

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Gastric cancer: a comprehensive review of current and future treatment strategies

Sexton

Hallak

Diab

et al. 2020

Cancer Metastasis Rev

406

251

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Gastric cancer remains a major unmet clinical problem with over 1 million new cases worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such as H. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year survival for stage IA and IB tumors treated with surgery are between 60 and 80%. However, patients with stage III tumors undergoing surgery have a dismal 5-year survival rate between 18 and 50% depending on the dataset. These figures indicate the need for more effective molecularly driven treatment strategies. This review discusses the molecular profile of gastric tumors, the success, and challenges with available therapeutic targets along with newer biomarkers and emerging targets.

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Section: Cancer-associated Fibroblasts and Angiogenesismentioning

confidence: 99%

Section: Cancer-associated Fibroblasts and Angiogenesismentioning

confidence: 99%

Gastric cancer: a comprehensive review of current and future treatment strategies

Sexton

Hallak

Diab

et al. 2020

Cancer Metastasis Rev

406

251

View full text Add to dashboard Cite

show abstract

“…Then, we used TGF-β1 at the optimal concentration of 5 ng/ml (Figure S2A-D) to stimulate HPF-a cells and veri ed that GREM1 expression rst increased and then decreased in a time-dependent manner, reaching a peak at 1 h (Figure 3H and I). Many studies have examined the function of Grem1 in brosis [16,17,18,19], but its mechanism is still unclear, and we will mainly discuss the mechanism by which Grem1 causes pulmonary brosis. We generated a bubble chart of the signaling pathways related to the occurrence and development of brosis (Figure 3J) and performed protein network interaction analysis (PPI) on the genes in these signaling pathways to identify speci c targets of brosis (Figure 3K).…”

Section: Analysis Of Broblast Subtypesmentioning

confidence: 99%

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

Shi¹,

Yang²,

Luo³

et al. 2021

Preprint

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Background: Fibroblasts have important roles in the synthesis and remodeling of extracellular matrix (ECM) proteins during pulmonary fibrosis. However, the spatiotemporal distribution of heterogeneous fibroblasts during disease progression remains unknown. Methods: Physiological saline and silica were used to generate a chronic pulmonary fibrosis model in mice, and single-cell sequencing, spatial transcriptome sequencing, real-time fluorescent quantitative PCR, immunohistochemistry and immunofluorescence were performed to identify fibroblast subtypes. Small interfering RNA was used to specifically knockdown the target protein, and western blotting, bromodeoxyuridine (BrdU), Cell Counting Kit-8 (CCK-8) and wound healing assays were used to detect the role of GREM1/PPP2R3A in a newly identified fibroblast subtype. Results: Fibroblasts of the new subtype were mainly located in the lesion area and coexpressed inflammation- and proliferation-related genes; they were termed inflammatory-proliferation fibroblasts. Grem1 was the most highly expressed gene in this subtype, as confirmed in HPF-a cells after TGF-β1 treatment. We characterized the downstream mechanism of GREM1/PPP2R3A: these factors mediated the increases in cell viability, proliferation and migration induced by TGF-β1 in fibroblasts. Conclusion: This new subtype of inflammatory, proliferative fibroblasts plays a pivotal role during pulmonary fibrosis, and PPP2R3A, as a downstream regulatory target of GREM1, is involved in pulmonary fibrosis, providing new insights for the prevention and treatment of silicosis.

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“…Physiologically, EMT can be observed during embryogenesis, tissue development and wound healing [48]. It is also a common phenomenon during carcinogenesis and can either induce or coexist with various malignancies such as breast cancer, thyroid cancer, cholangiocarcinoma, non-small cell lung carcinoma, colorectal cancer, inflammatory bowel disease or GC [49][50][51][52][53][54][55][56][57][58][59][60]. During the EMT process, ECs undergo a series of biochemical reactions that eventually lead to alterations in the cells' morphology, especially the loss of the polarity of cells [17,61].…”

Section: Figurementioning

confidence: 99%

“…Neutrophils can induce EMT in tumor cells, thereby increasing the migratory ability and invasiveness of GC cells [87]. Not only the elevated absolute peripheral blood neutrophil counts but also the neutrophil/lymphocyte ratio, and neutrophil infiltration in the tumor microenvironment, all make up for poor prognosis [55]. The neutrophil/lymphocyte ratio is a significant prognostic factor in GC progression.…”

Section: Tumor-associated Neutrophilsmentioning

confidence: 99%

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

Baj

Brzozowska

Forma

et al. 2020

IJMS

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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)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(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.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

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Increased Expression of Gremlin1 Promotes Proliferation and Epithelial Mesenchymal Transition in Gastric Cancer Cells and Correlates With Poor Prognosis of Patients With Gastric Cancer

Cited by 16 publications

References 46 publications

Gastric cancer: a comprehensive review of current and future treatment strategies

Gastric cancer: a comprehensive review of current and future treatment strategies

PPP2R3A Affects the Function and Mechanism of Heterogeneous Fibroblasts in Pulmonary Fibrosis

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

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