BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway

The JAK/STAT3 signaling pathway plays an essential role in various types of cancers. Activation of this pathway leads to increased tumorigenic and metastatic ability, the transition of cancer stem cells (CSCs), and chemoresistance in cancer via enhancing the epithelial–mesenchymal transition (EMT). EMT acts as a critical regulator in the progression of cancer and is involved in regulating invasion, spread, and survival. Furthermore, accumulating evidence indicates the failure of conventional therapies due to the acquisition of CSC properties. In this review, we summarize the effects of JAK/STAT3 activation on EMT and the generation of CSCs. Moreover, we discuss cutting-edge data on the link between EMT and CSCs in the tumor microenvironment that involves a previously unknown function of miRNAs, and also discuss new regulators of the JAK/STAT3 signaling pathway.

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Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1239-3 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 21

Author(s):

Dong-Mei Wu ◽

Zi-Hui Zheng ◽

Ying-Bo Zhang ◽

Shao-Hua Fan ◽

Zi-Feng Zhang ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Signaling Pathway ◽

Promoter Methylation ◽

Liver Cancer Stem Cells ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway

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Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

International Journal of Veterinary Science ◽

10.37422/ijvs/20.043 ◽

2020 ◽

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Helicobacter Pylori ◽

Cancer Stem Cells ◽

Histopathological Examination ◽

Physiological Saline ◽

Rrna Gene ◽

Peptic Ulcers ◽

Gastric Cancer Stem Cells ◽

H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

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STAM2 knockdown inhibits proliferation, migration, and invasion by affecting the JAK2/STAT3 signaling pathway in gastric cancer

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab038 ◽

2021 ◽

Author(s):

Yang Yang ◽

Q i Zhang ◽

Jiakui Liang ◽

Meiyuan Yang ◽

Zheng Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Signaling Pathway ◽

Mammalian Cells ◽

Migration And Invasion ◽

Boyden Chamber ◽

Pathway Enrichment Analysis ◽

Stat3 Signaling ◽

Advanced Tumor ◽

Stat3 Signaling Pathway ◽

Tumor Node Metastasis Stage

Abstract Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which regulates receptor signaling and trafficking of mammalian cells. However, its role in gastric cancer (GC) remains undiscovered. In this study, we aimed to investigate the functions of STAM2 in GC. The mRNA and protein expression levels of STAM2 were measured by quantitative real-time PCR, western blot analysis, and immunohistochemistry. STAM2 was stably silenced in AGS and HGC-27 cells using small interfering RNA. The function of STAM2 in GC cells was further investigated by CCK-8 assay, EdU incorporation assay, flow cytometry, and scratch wound healing and Boyden chamber assays. Additionally, we conducted biological pathway enrichment analysis and rescue assays to explore the effects of STAM2 on JAK/STAT signaling pathway. Our results showed that STAM2 is remarkably highly expressed in GC tissues and cells, and overexpressed STAM2 is correlated with tumor size, advanced tumor node metastasis stage, and poor prognosis. In addition, STAM2 knockdown could significantly inhibit proliferation, block cell cycle, and restrain migration and invasion capabilities of GC cells. Mechanistically, we found that STAM2 knockdown effectively decreased the expressions of MMP2 and MMP9 and the phosphorylation levels of JAK2 and STAT3. Taken together, this study revealed that STAM2 knockdown could suppress malignant process by targeting the JAK2/STAT3 signaling pathway in GC.

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