Carcinogenic Helicobacter pylori Strains Selectively Dysregulate the In Vivo Gastric Proteome, Which May Be Associated with Stomach Cancer Progression*

Noto, Jennifer M.; Rose, Kristie L.; Hachey, Amanda J.; Delgado, Alberto; Romero–Gallo, Judith; Wroblewski, Lydia E.; Schneider, Barbara; Shah, Shailja C.; Cover, Timothy L.; Wilson, Keith T.; Israel, Dawn A.; Roa, Juan Carlos; Schey, Kevin L.; Zavros, Yana; Piazuelo, M. Blanca; Peek, Richard M.

doi:10.1074/mcp.ra118.001181

Cited by 23 publications

(21 citation statements)

References 55 publications

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“…Interestingly, in BGC823 cells treated with or without J166 or 7.13 (two Cag + H. pylori strains) (Soutto et al , ), the expression of UHMK1 mRNA and protein was significantly upregulated (Fig A and B). When the Cag + H. pylori strain PMSS1 or Brucella broth (as the negative control) was used to challenge mice (Noto et al , ), PMSS1 infection significantly enhanced the levels of UHMK1 mRNA and protein compared to those in control mice (Fig C and D). Moreover, H. pylori infection significantly enhanced NCOA3 phosphorylation at S1062/T1067 but did not markedly affect the total levels of NCOA3 and ATF4 (Fig B and D).…”

Section: Resultsmentioning

confidence: 91%

UHMK 1 promotes gastric cancer progression through reprogramming nucleotide metabolism

Feng

Zhao

et al. 2020

The EMBO Journal

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UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1‐induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism‐associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC‐associated UHMK1 mutation induced NCOA3‐S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho‐NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1‐activated de novo purine synthesis pathway significantly promotes GC development.

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Section: Resultsmentioning

confidence: 91%

UHMK 1 promotes gastric cancer progression through reprogramming nucleotide metabolism

Feng

Zhao

et al. 2020

The EMBO Journal

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“…Based on a previous study [19], the labeling agent of the iTRAQ (Thermo, USA) kit was dissolved in acetonitrile buffer after thawing. Briefly, cell samples were harvested in lysis buffer (8 M urea and 1% protease inhibitor cocktail) and sonicated three times on ice with a high-intensity ultrasonic processor (Scientz, China).…”

Section: Itraq Proteomicsmentioning

confidence: 99%

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Xia

Cai

2020

Cell Mol Biol Lett

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Background: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown. Material and methods: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion. Results: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actinmyosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV. Conclusions: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer.

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“…14 By using protonography and mass spectrometry, Ronci et al 15 confirmed the presence of α-carbonic anhydrase (CA) in OMVs generated by planktonic and biofilm phenotypes of H pylori strains. 22 The study by Noto et al, 23 on gerbil and human gastric epithelium models, revealed that H pylori CagA + strains induced gastric proteomic changes, which were correlated with upregulation of Rab/Ras signaling proteins: RABEP2 and G3BP2, and the severity of malignant lesions in vivo. 15 According to Turner et al, 16 This study showed that it did not occur by altering toxin trafficking to lysosomes or autophagosomes but by increasing the intracellular VacA stability.…”

Section: Outer Membrane Vesiclesmentioning

confidence: 99%

“…This process allows polarized epithelial cells to differentiate into a mesenchymal phenotype with enhanced migration activity and invasiveness. 22 The study by Noto et al, 23 on gerbil and human gastric epithelium models, revealed that H pylori CagA + strains induced gastric proteomic changes, which were correlated with upregulation of Rab/Ras signaling proteins: RABEP2 and G3BP2, and the severity of malignant lesions in vivo.…”

Section: Vaca Caga and Related Virulence Factorsmentioning

confidence: 99%

Review: Pathogenesis of Helicobacter pylori infection

Chmiela

Kupčinskas

2019

Helicobacter

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In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins.

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Carcinogenic Helicobacter pylori Strains Selectively Dysregulate the In Vivo Gastric Proteome, Which May Be Associated with Stomach Cancer Progression*

Cited by 23 publications

References 55 publications

UHMK 1 promotes gastric cancer progression through reprogramming nucleotide metabolism

UHMK 1 promotes gastric cancer progression through reprogramming nucleotide metabolism

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Review: Pathogenesis of Helicobacter pylori infection

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