We are analyzing https://link.springer.com/article/10.1186/s12929-020-00638-x.

Title:
A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3—PBX1 and β-catenin—ABCG2 signaling | Journal of Biomedical Science
Description:
Background The underlying mechanism involved in ovarian cancer stemness and chemoresistance remains largely unknown. Here, we explored whether the regulation of c-Kit and plasma membrane prohibitin (PHB) affects ovarian cancer stemness and chemotherapy resistance. Methods Mass spectrum analysis and an in vitro kinase assay were conducted to examine the phosphorylation of PHB at tyrosine 259 by c-Kit. The in vitro effects of c-Kit on membrane raft-PHB in ovarian cancer were determined using tissue microarray (TMA)-based immunofluorescence, western blotting, immunoprecipitation, colony and spheroid formation, cell migration and cell viability assays. In vivo tumor initiation and carboplatin treatment were conducted in nude mice. Results We found that c-Kit and PHB colocalized in the raft domain and were positively correlated in human ovarian serous carcinoma. c-Kit interacted with PHB and facilitated the phosphorylation of PHB at tyrosine 259 (phospho-PHBY259) in the membrane raft to enhance ovarian cancer cell motility. The generation of SKOV3GL-G4, a metastatic phenotype of SKOV3 green fluorescent protein and luciferase (GL) ovarian cancer cells, in xenograft murine ascites showed a correlation between metastatic potential and stem cell characteristics, as indicated by the expression of c-Kit, Notch3, Oct4, Nanog and SOX2. Further study revealed that after activation by c-Kit, raft-phospho-PHBY259 interacted with Notch3 to stabilize Notch3 and increase the downstream target PBX1. Downregulation of raft-phospho-PHBY259 increased the protein degradation of Notch3 through a lysosomal pathway and inhibited the β-catenin—ABCG2 signaling pathway. Moreover, raft-phospho-PHBY259 played an important role in ovarian cancer stemness and tumorigenicity as well as resistance to platinum drug treatment in vitro and in vivo. Conclusions These findings thus reveal a hitherto unreported interrelationship between c-Kit and PHB as well as the effects of raft-phospho-PHBY259 on ovarian cancer stemness and tumorigenicity mediated by the Notch3 and β-catenin signaling pathways. Targeting the c-Kit/raft-phospho-PHBY259 axis may provide a new therapeutic strategy for treating patients with ovarian cancer.
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Keywords {🔍}

cells, ckit, cancer, ovarian, phb, pubmed, notch, fig, article, membrane, cell, skovglg, google, scholar, raft, cas, phosphophby, expression, domain, stem, skov, protein, signaling, usa, pdphbyfha, kinase, tumor, transfected, assay, carboplatin, central, western, skovckit, plasmid, analyzed, resistance, tyrosine, results, carcinoma, analysis, blotting, serous, skovgl, data, stemness, showed, raftphosphophby, lipid, antibody, vector,

Topics {✒️}

transfect plvx-ires-c-kit-puro plasmid plasmid plvx-ires-c-kit-puro c-kit/raft-phospho-phby259 axis wild-type pd-phb-ha plasmid pd-phbwt-ha enhanced β-catenin c-kit increases raft-phospho-phby259 wnt/β-catenin—abcg2 pathway [19] shu-mei liang c-kit-mediated phospho-phby259 results serum-free dmem/f12 medium wild-type pd-phb-ha targeting c-kit/raft-phospho-phby259 increase wnt/β-catenin signaling mutant pd-phby259f-ha reduced mutant pd-phby259f-ha plasmid β-catenin—abcg2 signaling pathway β-catenin—abcg2 signaling pathways raft-phospho-phby259-depleted cells c-kit upregulates phospho-phby259 c-kit-mediated phospho-phby259 high-grade serous adenocarcinomas c-kit-overexpressing tumor cells phospho-phby259 regulates phospho-phbt258 pd-phby259f-ha transfection reduced phb mutant pd-phby259f-ha raft-phospho-phby259-mediated regulation serous-type ovarian carcinoma platelet-derived growth factor vascular ligand-receptor mapping article download pdf cancer stemness-related notch3—pbx1 raft-phospho-phby259 reduced tumorigenicity rhodamine-tagged peptide ckggrakdc rhodamine-tagged ckggrakdc peptide prohibitin promotes de-differentiation stemness-related pathway notch3—pbx1 raft-phospho-phb protein expression β-catenin signaling pathway β-catenin signaling pathways ovarian cancer-initiating cells plasmid pd-phbwt-ha pd-phbwt-ha plasmid β-catenin—abcg2 signaling pd-phby259f-ha plasmids pd-phby259f-ha plasmid β-catenin-mediated upregulation c-kit-induced phb phosphorylation adp-glo kinase assay β-catenin—abcg2 pathway [19] overexpressing c-kit increased

Questions {❓}

EMT and MET in metastasis: where are the cancer stem cells?

Schema {🗺️}

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         description:The underlying mechanism involved in ovarian cancer stemness and chemoresistance remains largely unknown. Here, we explored whether the regulation of c-Kit and plasma membrane prohibitin (PHB) affects ovarian cancer stemness and chemotherapy resistance. Mass spectrum analysis and an in vitro kinase assay were conducted to examine the phosphorylation of PHB at tyrosine 259 by c-Kit. The in vitro effects of c-Kit on membrane raft-PHB in ovarian cancer were determined using tissue microarray (TMA)-based immunofluorescence, western blotting, immunoprecipitation, colony and spheroid formation, cell migration and cell viability assays. In vivo tumor initiation and carboplatin treatment were conducted in nude mice. We found that c-Kit and PHB colocalized in the raft domain and were positively correlated in human ovarian serous carcinoma. c-Kit interacted with PHB and facilitated the phosphorylation of PHB at tyrosine 259 (phospho-PHBY259) in the membrane raft to enhance ovarian cancer cell motility. The generation of SKOV3GL-G4, a metastatic phenotype of SKOV3 green fluorescent protein and luciferase (GL) ovarian cancer cells, in xenograft murine ascites showed a correlation between metastatic potential and stem cell characteristics, as indicated by the expression of c-Kit, Notch3, Oct4, Nanog and SOX2. Further study revealed that after activation by c-Kit, raft-phospho-PHBY259 interacted with Notch3 to stabilize Notch3 and increase the downstream target PBX1. Downregulation of raft-phospho-PHBY259 increased the protein degradation of Notch3 through a lysosomal pathway and inhibited the β-catenin—ABCG2 signaling pathway. Moreover, raft-phospho-PHBY259 played an important role in ovarian cancer stemness and tumorigenicity as well as resistance to platinum drug treatment in vitro and in vivo. These findings thus reveal a hitherto unreported interrelationship between c-Kit and PHB as well as the effects of raft-phospho-PHBY259 on ovarian cancer stemness and tumorigenicity mediated by the Notch3 and β-catenin signaling pathways. Targeting the c-Kit/raft-phospho-PHBY259 axis may provide a new therapeutic strategy for treating patients with ovarian cancer.
         datePublished:2020-03-13T00:00:00Z
         dateModified:2020-03-13T00:00:00Z
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            Prohibitin
            Notch3
            β-catenin
            Cancer stem cells
            Lipid raft domain of plasma membrane
            Biomedicine
            general
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      headline:A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3—PBX1 and β-catenin—ABCG2 signaling
      description:The underlying mechanism involved in ovarian cancer stemness and chemoresistance remains largely unknown. Here, we explored whether the regulation of c-Kit and plasma membrane prohibitin (PHB) affects ovarian cancer stemness and chemotherapy resistance. Mass spectrum analysis and an in vitro kinase assay were conducted to examine the phosphorylation of PHB at tyrosine 259 by c-Kit. The in vitro effects of c-Kit on membrane raft-PHB in ovarian cancer were determined using tissue microarray (TMA)-based immunofluorescence, western blotting, immunoprecipitation, colony and spheroid formation, cell migration and cell viability assays. In vivo tumor initiation and carboplatin treatment were conducted in nude mice. We found that c-Kit and PHB colocalized in the raft domain and were positively correlated in human ovarian serous carcinoma. c-Kit interacted with PHB and facilitated the phosphorylation of PHB at tyrosine 259 (phospho-PHBY259) in the membrane raft to enhance ovarian cancer cell motility. The generation of SKOV3GL-G4, a metastatic phenotype of SKOV3 green fluorescent protein and luciferase (GL) ovarian cancer cells, in xenograft murine ascites showed a correlation between metastatic potential and stem cell characteristics, as indicated by the expression of c-Kit, Notch3, Oct4, Nanog and SOX2. Further study revealed that after activation by c-Kit, raft-phospho-PHBY259 interacted with Notch3 to stabilize Notch3 and increase the downstream target PBX1. Downregulation of raft-phospho-PHBY259 increased the protein degradation of Notch3 through a lysosomal pathway and inhibited the β-catenin—ABCG2 signaling pathway. Moreover, raft-phospho-PHBY259 played an important role in ovarian cancer stemness and tumorigenicity as well as resistance to platinum drug treatment in vitro and in vivo. These findings thus reveal a hitherto unreported interrelationship between c-Kit and PHB as well as the effects of raft-phospho-PHBY259 on ovarian cancer stemness and tumorigenicity mediated by the Notch3 and β-catenin signaling pathways. Targeting the c-Kit/raft-phospho-PHBY259 axis may provide a new therapeutic strategy for treating patients with ovarian cancer.
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      dateModified:2020-03-13T00:00:00Z
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      pageEnd:18
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         c-Kit
         Prohibitin
         Notch3
         β-catenin
         Cancer stem cells
         Lipid raft domain of plasma membrane
         Biomedicine
         general
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      affiliation:
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            address:
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               type:PostalAddress
            type:Organization
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      affiliation:
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      name:Institute of Biotechnology, National Taiwan University, Taipei, Taiwan
      name:Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
      name:Genomics Research Center, Academia Sinica, Taipei, Taiwan
      name:Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
      name:Institute of Biotechnology, National Taiwan University, Taipei, Taiwan

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