We are analyzing https://link.springer.com/article/10.1007/s10120-020-01068-2.

Title:
Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells | Gastric Cancer
Description:
Background Gastrokine 1 (GKN1) is a stomach-specific tumor suppressor that is secreted into extracellular space as an exosomal cargo protein. The objective of this study was to investigate the uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells. Methods Immunofluorescent and Western blot analysis were used to investigate gastric-specific uptake of HFE-145-derived exosomes. Binding affinity of HFE-145 derived exosomes with integrin proteins was examined using protein microarray chip. Tumor suppressor activities of exosome-carrying GKN1 protein were analyzed using transwell co-culture, MTT assay, BrdU incorporation, immunoprecipitation, and Western blot analysis. Results HFE-145-derived exosomes were internalized only into HFE-145 gastric epithelial cells and gastric cancer cells. Gastric-specific uptake of stomach-derived exosomes required integrin α6 and αX proteins. Clathrin and macropinocytosis increased the uptake of exosomes into gastric epithelial cells, whereas caveolin inhibited the uptake of exosomes. Transwell co-culture of AGS cells with HFE-145 cells markedly inhibited viability and proliferation of AGS cells. Following uptake of HFE-145-derived exosomes in recipient cells, GKN1 protein bound to HRas and inhibited the binding of HRas to b-Raf and c-Raf which subsequently downregulated HRas/Raf/MEK/ERK signaling pathways in AGS, MKN1 cells, and MKN1-derived xenograft tumor tissues. In addition, exosomal GKN1 protein suppressed both migration and invasion of gastric cancer cells by inhibiting epithelial–mesenchymal transition. Conclusions Gastric-specific uptake of exosomes derived from gastric epithelial cells requires integrin α6 and αX proteins in both gastric epithelial cells and exosomes. Exosomal GKN1 protein inhibits gastric carcinogenesis by downregulating HRas/Raf/MEK/ERK signaling pathways.
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Keywords {🔍}

cells, exosomes, gastric, ags, hfe, cancer, gkn, expression, protein, mkn, derived, epithelial, integrin, fig, article, pubmed, uptake, proteins, cell, google, scholar, cas, caveolin, hras, ras, treated, binding, inhibited, levels, signaling, internalization, snu, clathrin, exosome, tissues, analysis, bound, addition, knockdown, gknδ, braf, craf, domain, pathway, epub, tumor, transwell, reduced, central, lung,

Topics {✒️}

ras/raf/mek/erk signaling pathway ras/raf/mek/erk kinase cascade hras/raf/mek/erk signaling pathway hras/raf/mek/erk signaling pathways epstein-barr virus-infected cells raf/mek/erk pathway gst–raf1–rbd fusion protein full size image serine/threonine protein kinase nf-kappab-inducing kinase won sang park stomach-specific tumor suppressor inhibiting epithelial–mesenchymal transition nh2-terminal hydrophophic region nh2-terminal hydrophobic region induce organ-specific colonization pylori caga-induced overexpression hfe-145-derived exosome-treated cells membrane-bound extracellular vesicles n-ethyl-n-isopropyl increased e-cadherin expression turn activates ras-gtp signaling pathways involved epithelial–mesenchymal transition epithelial-mesenchymal transition recipient cell-dependent differences mek/erk activation [33] suk woo nam caveolin-mediated endocytosis modulated tumor suppressor activities nf-kappab pathway article yoon exosome-carrying gkn1 protein mediating mir-21 delivery ikappab kinase alpha yoon jh transwell cell-culture inserts xenograft tumors treated tumor-suppressive pathways cell signaling technology xenograft tumors tissues investigate gastric-specific uptake normal cell-derived exosomes tumor suppressor roles gastric epithelial cells inhibit gastric carcinogenesis immunoprecipitation assay showed privacy choices/manage cookies related subjects emt-related proteins

Schema {🗺️}

WebPage:
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         headline:Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells
         description:Gastrokine 1 (GKN1) is a stomach-specific tumor suppressor that is secreted into extracellular space as an exosomal cargo protein. The objective of this study was to investigate the uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells. Immunofluorescent and Western blot analysis were used to investigate gastric-specific uptake of HFE-145-derived exosomes. Binding affinity of HFE-145 derived exosomes with integrin proteins was examined using protein microarray chip. Tumor suppressor activities of exosome-carrying GKN1 protein were analyzed using transwell co-culture, MTT assay, BrdU incorporation, immunoprecipitation, and Western blot analysis. HFE-145-derived exosomes were internalized only into HFE-145 gastric epithelial cells and gastric cancer cells. Gastric-specific uptake of stomach-derived exosomes required integrin α6 and αX proteins. Clathrin and macropinocytosis increased the uptake of exosomes into gastric epithelial cells, whereas caveolin inhibited the uptake of exosomes. Transwell co-culture of AGS cells with HFE-145 cells markedly inhibited viability and proliferation of AGS cells. Following uptake of HFE-145-derived exosomes in recipient cells, GKN1 protein bound to HRas and inhibited the binding of HRas to b-Raf and c-Raf which subsequently downregulated HRas/Raf/MEK/ERK signaling pathways in AGS, MKN1 cells, and MKN1-derived xenograft tumor tissues. In addition, exosomal GKN1 protein suppressed both migration and invasion of gastric cancer cells by inhibiting epithelial–mesenchymal transition. Gastric-specific uptake of exosomes derived from gastric epithelial cells requires integrin α6 and αX proteins in both gastric epithelial cells and exosomes. Exosomal GKN1 protein inhibits gastric carcinogenesis by downregulating HRas/Raf/MEK/ERK signaling pathways.
         datePublished:2020-04-06T00:00:00Z
         dateModified:2020-04-06T00:00:00Z
         pageStart:848
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            GKN1
            Exosome
            Uptake
            Ras signaling
            Gastric cancer
            Surgical Oncology
            Oncology
            Abdominal Surgery
            Gastroenterology
            Cancer Research
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      headline:Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells
      description:Gastrokine 1 (GKN1) is a stomach-specific tumor suppressor that is secreted into extracellular space as an exosomal cargo protein. The objective of this study was to investigate the uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells. Immunofluorescent and Western blot analysis were used to investigate gastric-specific uptake of HFE-145-derived exosomes. Binding affinity of HFE-145 derived exosomes with integrin proteins was examined using protein microarray chip. Tumor suppressor activities of exosome-carrying GKN1 protein were analyzed using transwell co-culture, MTT assay, BrdU incorporation, immunoprecipitation, and Western blot analysis. HFE-145-derived exosomes were internalized only into HFE-145 gastric epithelial cells and gastric cancer cells. Gastric-specific uptake of stomach-derived exosomes required integrin α6 and αX proteins. Clathrin and macropinocytosis increased the uptake of exosomes into gastric epithelial cells, whereas caveolin inhibited the uptake of exosomes. Transwell co-culture of AGS cells with HFE-145 cells markedly inhibited viability and proliferation of AGS cells. Following uptake of HFE-145-derived exosomes in recipient cells, GKN1 protein bound to HRas and inhibited the binding of HRas to b-Raf and c-Raf which subsequently downregulated HRas/Raf/MEK/ERK signaling pathways in AGS, MKN1 cells, and MKN1-derived xenograft tumor tissues. In addition, exosomal GKN1 protein suppressed both migration and invasion of gastric cancer cells by inhibiting epithelial–mesenchymal transition. Gastric-specific uptake of exosomes derived from gastric epithelial cells requires integrin α6 and αX proteins in both gastric epithelial cells and exosomes. Exosomal GKN1 protein inhibits gastric carcinogenesis by downregulating HRas/Raf/MEK/ERK signaling pathways.
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      dateModified:2020-04-06T00:00:00Z
      pageStart:848
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         GKN1
         Exosome
         Uptake
         Ras signaling
         Gastric cancer
         Surgical Oncology
         Oncology
         Abdominal Surgery
         Gastroenterology
         Cancer Research
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      name:Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
      name:Department of Surgery, Brain Korea 21 Plus Research Center for Biomedical Science, Ajou University School of Medicine, Suwon, South Korea
      name:Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea

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