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ABC Transporters

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A Rangarajan – One of the best experts on this subject based on the ideXlab platform.

  • transcription factors that mediate epithelial mesenchymal transition lead to multidrug resistance by upregulating ABC Transporters
    Cell Death and Disease, 2011
    Co-Authors: M Saxena, M A Stephens, H Pathak, A Rangarajan
    Abstract:

    Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette Transporters (ABC Transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC Transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC Transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC Transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC Transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC Transporters. Thus, our study identifies EMT inducers as novel regulators of ABC Transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.

  • Transcription factors that mediate epithelial–mesenchymal transition lead to multidrug resistance by upregulating ABC Transporters
    Cell Death & Disease, 2011
    Co-Authors: M Saxena, M A Stephens, H Pathak, A Rangarajan
    Abstract:

    Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette Transporters (ABC Transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC Transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC Transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC Transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC Transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC Transporters. Thus, our study identifies EMT inducers as novel regulators of ABC Transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.

Barbara Papadopoulou – One of the best experts on this subject based on the ideXlab platform.

  • ABC Transporters in Leishmania and their role in drug resistance.
    Drug Resistance Updates, 1998
    Co-Authors: Marc Ouellette, Danielle Légaré, Anass Haimeur, Katherine Grondin, Christian Brochu, Barbara Papadopoulou
    Abstract:

    Abstract ABC Transporters have been found in several parasitic protozoa including Leishmania . At least two Leishmania ABC Transporters are involved in drug resistance. One is PgpA, which is involved in resistance to arsenic and antimony-containing compounds. Antimonials are the drug of choice against Leishmania infections. Transfection and biochemical studies suggest that PgpA recognizes metals conjugated to thiols. The second ABC transporter is closely related to mammalian P-glycoproteins and confers resistance to anticancer drugs by a mechanism that remains to be elucidated. Additional ABC Transporters are likely to be present in Leishmania and these are discussed in relation to the phenomenon of antimony resistance.

  • Microbial multidrug-resistance ABC Transporters
    Trends in Microbiology, 1994
    Co-Authors: Marc Ouellette, Danielle Légaré, Barbara Papadopoulou
    Abstract:

    Abstract Multidrug resistance in tumor cells is often caused by the increased efflux of a wide variety of drugs, mediated by P glycglycoprotein, a member of the superfamily of ATP-binding cassette (ABC) Transporters. The genes encoding members of this superfamily have also been isolated from drug-resistant microorganisms, and the role of microbial ABC Transporters in drug resistance is being investigated.

Helmut Segner – One of the best experts on this subject based on the ideXlab platform.

  • ABC Transporters in gills of rainbow trout (Oncorhynchus mykiss).
    The Journal of Experimental Biology, 2020
    Co-Authors: Christian Kropf, Karl Fent, Stephan Fischer, Ayako Casanova, Helmut Segner
    Abstract:

    Fish gills are a structurally and functionally complex organ at the interface between organism and the aquatic environment. Gill functions include the transfer of organic molecules, both natural ones and xenobiotic compounds. Whether the branchial exchange of organic molecules involves active Transporters is currently not known. Here, we investigated the presence, diversity, and functional activity of ATP-binding cassette (ABC) Transporters in gills of juvenile rainbow trout. By means of RT-qPCR, gene transcripts of members from the ABCb, ABCc and ABCg subfamilies were identified. Comparisons with mRNA profiles from trout liver and kidney revealed that ABC Transporters known for an apical localization in polarized epithelia, especially ABCc2 and ABCb1 were underrepresented in the gills. In contrast, ABC Transporters with mainly basolateral localization showed comparable gene transcript levels in the three organs. The most prominent ABC transporter in gills was an ABCb subfamily member, which was annotated as ABCb5 based on the synteny and phylogeny. Functional in vivo assays pointed to a role of branchial ABC Transporters in branchial solute exchange. We further assessed the utility of primary gill cell cultures to characterize transporter-mediated branchial exchange of organic molecules, we examined ABC transporter gene transcript patterns and functional activity in primary cultures. The cultures display functional transport activity, but the ABC mRNA expression patterns were different to those of the intact gills. Overall, the findings of this study provide evidence for the presence of functional ABC transporter activity in gills of fish.

Geoffrey Chang – One of the best experts on this subject based on the ideXlab platform.

M Saxena – One of the best experts on this subject based on the ideXlab platform.

  • transcription factors that mediate epithelial mesenchymal transition lead to multidrug resistance by upregulating ABC Transporters
    Cell Death and Disease, 2011
    Co-Authors: M Saxena, M A Stephens, H Pathak, A Rangarajan
    Abstract:

    Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette Transporters (ABC Transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC Transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC Transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC Transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC Transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC Transporters. Thus, our study identifies EMT inducers as novel regulators of ABC Transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.

  • Transcription factors that mediate epithelial–mesenchymal transition lead to multidrug resistance by upregulating ABC Transporters
    Cell Death & Disease, 2011
    Co-Authors: M Saxena, M A Stephens, H Pathak, A Rangarajan
    Abstract:

    Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette Transporters (ABC Transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC Transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC Transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC Transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC Transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC Transporters. Thus, our study identifies EMT inducers as novel regulators of ABC Transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.