Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Curr Biol ; 32(10): 2144-2159.e5, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35417667

RESUMO

For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extracellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an "extrude me" signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.


Assuntos
Apoptose , Competição entre as Células , Trifosfato de Adenosina/metabolismo , Células Epiteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Nat Cell Biol ; 19(5): 530-541, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28414314

RESUMO

Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the surrounding normal cells, involving filamin, drives the Warburg-effect-like metabolic alteration. Moreover, using a cell-competition mouse model, we demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12-transformed cells from intestinal epithelia. These data indicate that non-cell-autonomous metabolic modulation is a crucial regulator for cell competition, shedding light on the unexplored events at the initial stage of carcinogenesis.


Assuntos
Comunicação Celular , Transformação Celular Neoplásica/metabolismo , Metabolismo Energético , Células Epiteliais/metabolismo , Animais , Linhagem Celular Transformada , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Técnicas de Cocultura , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Cães , Feminino , Genes ras , Glucose/metabolismo , Glicólise , Ácido Láctico/metabolismo , Células Madin Darby de Rim Canino , Masculino , Potencial da Membrana Mitocondrial , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Interferência de RNA , Transdução de Sinais , Técnicas de Cultura de Tecidos , Transfecção
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...