Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic factors, Helicobacter pylori infection, salt over-uptake, decreased vegetable/fruit consumption, smoking, and metabolic syndrome are risk factors of human gastric cancer. Germline mutations of CDH1 gene, and SNPs of PTPN11 (SHP2), TLR4, IL1B, TNFA, BMP6, GDF15 and RUNX3 genes are associated with gastric cancer. Helicobacter pylori activates CagA-SHP2-ERK and peptidoglycan-NOD1-NFkappaB signaling cascades in gastric epithelial cells using type IV secretion system, and also TRAF6-MAP3K7-NFkappaB and TRAF6-MAP3K7-AP-1 signaling cascades in epithelial and immune cells through lipopolysaccharide recognition by TLR2 or TLR4. IL-1beta, IL-6, IL-8, TNFalpha and IFNgamma are elevated in gastric mucosa with Helicobacter pylori infection. IL-6 and TNFalpha induce upregulation of WNT5A and WNT10B, respectively. WNT signals are transduced to beta-catenin-TCF/LEF, RhoA, JNK, PKC, NFAT, and NLK signaling cascades. WNT-beta-catenin-TCF/LEF signaling induces upregulation of MYC, CCND1, WISP1, FGF20, JAG1 and DKK1 genes. Notch signals are transduced to CSL-NICD-MAML and NFkappaB signaling cascades. FGF signals are transduced to ERK, PI3K-AKT, PKC, and NFAT signaling cascades. Helicobacter pylori infection induces SHH upregulation in parietal cell lineage, while BMP signals induce IHH upregulation in pit cell lineage. Hedgehog signals induce upregulation of GLI1, PTCH1, CCND2, FOXL1, JAG2 and SFRP1 genes. JAG1 and JAG2 activate Notch signaling, while DKK1 and SFRP1 inhibit WNT signaling. Stem cell signaling network, consisting of WNT, Notch, FGF, Hedgehog and BMP signaling pathways, is activated during chronic Helicobacter pylori infection. Epigenetic silencing of SFRP1 gene occurs in the earlier stage of carcinogenesis in the stomach, while amplification and overexpression of FGFR2 gene in the later stage. Dysregulation of the stem cell signaling network due to the accumulation of germline mutation, SNP, Helicobacter pylori infection, epigenetic change and genetic alteration gives rise to gastric cancer. SNP typing and custom-made microarray analyses on genes encoding stem cell signaling molecules could be utilized for the personalized medicine.
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PMID:Dysregulation of stem cell signaling network due to germline mutation, SNP, Helicobacter pylori infection, epigenetic change and genetic alteration in gastric cancer. 1756 83

Gastric cancer is a malignant disease that arises from the gastric epithelium. A potential biomarker for gastric cancer is the protein annexin A4 (ANXA4), an intracellular Ca(2+) sensor. ANXA4 is primarily found in epithelial cells, and is known to be involved in various biological processes, including apoptosis, cell cycling and anticoagulation. In respect to cancer, ANXA4-overexpression has been observed in cancers of various origins, including gastric tumors associated with Helicobacter pylori infection. H. pylori induces ANXA4 expression and intracellular [Ca(2+)](i) elevation, and is an important risk factor for carcinogenesis that results in gastric cancer. Despite this correlation, the role of ANXA4 in the progression of gastric tumors remains unclear. In this study, we have investigated whether ANXA4 can mediate the rate of cell growth and whether ANXA4 downstream signals are involved in tumorigenesis. After observing the rate of cell growth in real-time, we determined that ANXA4 promotes cell proliferation. The transcription gene profile of ANXA4-overexpressing cells was measured and analyzed by human exon arrays. From this transcriptional gene data, we show that overexpression of ANXA4 regulates genes that are known to be related to cancer, for example the activation of hyaluronan mediated motility receptor (RHAMM), AKT, and cyclin-dependent kinase 1 (CDK1) as well as the suppression of p21. The regulation of these genes further induces cancer cell proliferation. We also found Ca(2+) could regulate the transmission of downstream signals by ANXA4. We suggest that ANXA4 triggers a signaling cascade, leading to increased epithelial cell proliferation, ultimately promoting carcinogenesis. These results might therefore provide a new insight for gastric cancer therapy, specifically through the modification of ANXA4 activity.
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PMID:Revealing the molecular mechanism of gastric cancer marker annexin A4 in cancer cell proliferation using exon arrays. 2297 Feb 68

This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model.
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PMID:Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer. 2757 85

Helicobacter pylori infection is strongly associated with primary gastric diseases, such as extranodal mucosa-associated lymphoid tissue (MALT) lymphoma, diffuse large B-cell lymphoma (DLBCL) with histologic evidence of MALT origin, and gastric carcinoma. The cytotoxin-associated gene A (CagA) protein behaves as a bacterial oncoprotein, promoting tumorigenesis via dysregulation of the phosphatidylinositol 3-kinase/AKT pathway (PI3K/AKT). We investigated the molecular mechanisms of PI3K/AKT pathway dysregulation in H. pylori-induced MALT and DLBCL gastric lymphoma. Immunohistochemical assays for CagA, phospho(p)-S473-AKT, PTEN, SHIP, and cyclin A2 proteins were performed on samples from 23 patients with H. pylori-positive MALT lymphoma and 16 patients with H. pylori-positive gastric DLBCL. We showed that CagA localization is correlated with the activation of the AKT pathway in both MALT and DLBCL lymphoma cells. Interestingly, we found a close association between the loss of PTEN, the overexpression of cyclin A2, and the phosphorylation of AKT in gastric MALT and DLBCL tumor cells.
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PMID:PTEN Loss and Cyclin A2 Upregulation Define a PI3K/AKT Pathway Activation in Helicobacter pylori-induced MALT and DLBCL Gastric Lymphoma With Features of MALT. 3213 55