Molecular and Functional Characterization of Choline Transporter-Like Proteins in Esophageal Cancer Cells and Potential Therapeutic Targets
Biomolecules & Therapeutics
;
: 399-408, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-715614
ABSTRACT
In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [3H]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both Na+-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
S-Adenosilmetionina
/
RNA Mensageiro
/
Neoplasias Esofágicas
/
Linhagem Celular
/
Membrana Celular
/
Sobrevivência Celular
/
Colina
/
Deficiência de Colina
/
Morte Celular
/
Metilação de DNA
Limite:
Humanos
Idioma:
Inglês
Revista:
Biomolecules & Therapeutics
Ano de publicação:
2018
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS