Publicação
Study of the metabolic conditions involved in monocarboxylate transporter MCT1 internalization in human cancer cell lines
| Resumo: | Cancer is a complex disease that represents a vast problem worldwide due to its high incidence and mortality, being the second leading cause of death globally. Even with the decrease of mortality in many countries, the incidence of this disease will increase, causing serious problems even in countries where health systems are more advanced. So, efforts have been made in order to identify new-targeted therapies. In the past decade, it has been reported that the monocarboxylate transporter MCT1 is highly expressed in multiple cancer types. MCT1 is a symporter that is responsible for the influx of lactate across the cell membrane and, in cancer cells, it supplies their metabolism and their rapid proliferation and expansion. This makes it a potential target molecule for therapy as well as a useful prognostic factor. This project aimed at evaluating the expression and localization of the EGFP-MCT1 transporter, by confocal microscopy, in U2OS cells, edited by the CRISPR-Cas9 technology, and grown under different metabolic conditions or in the presence of specific compounds. In this work we show that the EGFP-MCT1 transporter remains stable at the plasma membrane, in cells incubated in a medium without glucose or glutamine. These results highlight the relevance of expressing nutrient transporters at an endogenous level to study their intracellular trafficking. Additionally, our preliminary studies suggest the involvement of the Wnt signaling pathway in MCT1 internalization. We found that the presence of lithium chloride (LiCl), an activator of the Wnt pathway, also seems to lead to an increased MCT1 internalization, after 24 h of incubation. The results obtained in this study will contribute towards a better understanding of the molecular mechanisms involved in the expression and endocytic regulation of MCT1, and open novel therapeutic possibilities in the fight against tumors. |
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| Autores principais: | Pinto, Jéssica Patrícia Azevedo |
| Assunto: | Cancer Fluorescence microscopy Lactate MCT1 Metabolic reprogramming Monocarboxylate transporters Cancro Lactato Microscopia de fluorescência Reprogramação metabólica Transportadores de monocarboxilatos |
| Ano: | 2021 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Cancer is a complex disease that represents a vast problem worldwide due to its high incidence and mortality, being the second leading cause of death globally. Even with the decrease of mortality in many countries, the incidence of this disease will increase, causing serious problems even in countries where health systems are more advanced. So, efforts have been made in order to identify new-targeted therapies. In the past decade, it has been reported that the monocarboxylate transporter MCT1 is highly expressed in multiple cancer types. MCT1 is a symporter that is responsible for the influx of lactate across the cell membrane and, in cancer cells, it supplies their metabolism and their rapid proliferation and expansion. This makes it a potential target molecule for therapy as well as a useful prognostic factor. This project aimed at evaluating the expression and localization of the EGFP-MCT1 transporter, by confocal microscopy, in U2OS cells, edited by the CRISPR-Cas9 technology, and grown under different metabolic conditions or in the presence of specific compounds. In this work we show that the EGFP-MCT1 transporter remains stable at the plasma membrane, in cells incubated in a medium without glucose or glutamine. These results highlight the relevance of expressing nutrient transporters at an endogenous level to study their intracellular trafficking. Additionally, our preliminary studies suggest the involvement of the Wnt signaling pathway in MCT1 internalization. We found that the presence of lithium chloride (LiCl), an activator of the Wnt pathway, also seems to lead to an increased MCT1 internalization, after 24 h of incubation. The results obtained in this study will contribute towards a better understanding of the molecular mechanisms involved in the expression and endocytic regulation of MCT1, and open novel therapeutic possibilities in the fight against tumors. |
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