Effect of STAT3 inhibition on the metabolic switch in a highly STAT3-activated lymphoma cell line.
Cancer Genomics Proteomics
; 12(3): 133-42, 2015.
Article
em En
| MEDLINE
| ID: mdl-25977172
ABSTRACT
BACKGROUND:
Signal transducer and activator of transcription (STAT)3 is involved in a metabolic shift in cancer cells, the Warburg effect through its pro-oncogenic activity. To develop efficient STAT3 inhibitors against cancer cells, novel proteomic and metabolic target molecules need to be explored using multi-omics approaches in the context of STAT3 gene inhibition-mediated tumor growth suppression. MATERIALS ANDMETHODS:
We found that short hairpin (sh)RNA-mediated STAT3 inhibition suppressed tumor growth in a highly STAT3-activated lymphoma cell line, SCC-3 cells, and we investigated the effect of STAT3 inhibition on metabolic switching using 2-dimensional differential gel electrophoresis and capillary electrophoresis-time of flight-mass spectrometry.RESULTS:
We identified latexin as a proteomic marker candidate and metabolic enzymes including fructose-bisphosphate aldolase A (ALDOA) as a metabolic marker candidate for STAT3-targeting therapy using STAT3-specific shRNA gene transduction. In particular, latexin expression was up-regulated in four STAT3-activated cancer cell lines including SCC-3 transduced with STAT3-specific shRNA. The up-regulation of latexin was identified in SCC-3 tumors transplanted to nude mice after treatment with STAT3 inhibitor.CONCLUSION:
Our results suggest that STAT3 inactivation reverses the glycolytic shift by down-regulating key enzymes and that it induces up-regulation of latexin as a tumor-suppressor molecule, which partially results in cancer cell apoptosis and tumor growth suppression.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição STAT3
/
Metaboloma
/
Metabolômica
/
Linfoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cancer Genomics Proteomics
Assunto da revista:
BIOQUIMICA
/
GENETICA MEDICA
/
NEOPLASIAS
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Japão