Transcription factors that mediate epithelial–mesenchymal transition lead to multidrug resistance by upregulating ABC transporters

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

Plasmonic-enhanced polymer solar cells incorporating solution-processable Au nanoparticle-adhered graphene oxide

The effect of gold nanoparticle (NP)-induced surface plasmons on the performance of polymer solar cells (PSCs) is investigated by blending the solution processable Au NP-adhered graphene oxide (Au-GO) into the anodic buffer layer of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The incorporation of Au-GOs provides a simple method to introduce a plasmonic effect, which is helpful to avoid aggregation of Au NPs blended in PEDOT:PSS. The addition of Au-GOs increased the light absorption and exciton generation rate in the active layer, thereby enhancing the short-circuit current and power conversion efficiency of these PSCs. According to the experimental and simulated results, the improvement in device performance can be ascribed to the near-field enhancement arising from the excitation of the localized surface plasmon resonance of Au-GOs along the active layer/PEDOT:PSS interface. Our work indicates the great potential of Au-GOs for high-efficiency plasmonic-enhanced PSC applications. © 2012 The Royal Society of Chemistry