Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acta Biochim Biophys Sin (Shanghai) ; 54(8): 1140-1147, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35880569

RESUMO

Abnormal metabolism is a major hallmark of cancer and has been validated as a therapeutic target. Adenine monophosphate-activated protein kinase (AMPK), an αßγ heterotrimer, performs essential functions in cancer progression due to its central role in maintaining the homeostasis of cellular energy. While the contributions of AMPKα and AMPKγ subunits to cancer development have been established, specific roles of AMPKß1 and AMPKß2 isoforms in cancer development are poorly understood. Here, we show the functions of AMPKß1 and AMPKß2 in colon cancer. Specifically, deletion of AMPKß1 or AMPKß2 leads to increased cell proliferation, colony formation, migration, and tumorigenesis in HCT116 and HT29 colon cancer cells. Interestingly, the AMPKß1 and AMPKß2 isoforms have slightly different effects on regulating cancer metabolism, as colon cancer cells with AMPKß1 knockout showed decreased rates of glycolysis-related oxygen consumption, while AMPKß2 deletion led to enhanced rates of oxygen consumption due to oxidative phosphorylation. These results demonstrate that functional AMPKß1 and AMPKß2 inhibit growth and tumorigenesis in colon cancer cells, suggesting their potential as effective targets for colon cancer therapy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias do Colo , Proteínas Quinases Ativadas por AMP/genética , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias do Colo/genética , Humanos , Isoformas de Proteínas
2.
Protein Pept Lett ; 29(7): 567-573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35546749

RESUMO

Protein tyrosine phosphatase receptor-type Q (PTPRQ), a member of the type III tyrosine phosphatase receptor (R3 PTPR) family, is composed of three domains, including 18 extracellular fibronectin type III (FN3) repeats, a transmembrane helix, and a cytoplasmic phosphotyrosine phosphatase (PTP) domain. PTPRQ was initially identified as a transcript upregulated in glomerular mesangial cells in a rat model of glomerulonephritis. Subsequently, studies found that PTPRQ has phosphotyrosine phosphatase and phosphatidylinositol phosphatase activities and can regulate cell proliferation, apoptosis, differentiation, and survival. Further in vivo studies showed that PTPRQ is necessary for the maturation of cochlear hair bundles and is considered a potential gene for deafness. In the recent two decades, 21 mutations in PTPRQ have been linked to autosomal recessive hearing loss (DFNB84) and autosomal dominant hearing loss (DFNA73). Recent mutations, deletions, and amplifications of PTPRQ have been observed in many types of cancers, which indicate that PTPRQ might play an essential role in the development of many cancers. In this review, we briefly describe PTPRQ structure and enzyme activity and focus on the correlation between PTPRQ and human disease. A profound understanding of PTPRQ could be helpful in the identification of new therapeutic targets to treat associated diseases.


Assuntos
Cóclea/metabolismo , Perda Auditiva , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Animais , Cóclea/crescimento & desenvolvimento , Fibronectinas , Perda Auditiva/genética , Humanos , Fosfatidilinositóis , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo , Ratos , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/química
3.
Anticancer Agents Med Chem ; 21(8): 949-962, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32951587

RESUMO

Chemoresistance, which leads to the failure of chemotherapy and further tumor recurrence, presents the largest hurdle for the success of anti-cancer therapy. In recent years, metformin, a widely used first-line antidiabetic drug, has attracted increasing attention for its anti-cancer effects. A growing body of evidence indicates that metformin can sensitize tumor responses to different chemotherapeutic drugs, such as hormone modulating drugs, anti-metabolite drugs, antibiotics, and DNA-damaging drugs via selective targeting of Cancer Stem Cells (CSCs), improving the hypoxic microenvironment, and by suppressing tumor metastasis and inflammation. In addition, metformin may regulate metabolic programming, induce apoptosis, reverse Epithelial to Mesenchymal Transition (EMT), and Multidrug Resistance (MDR). In this review, we summarize the chemosensitization effects of metformin and focus primarily on its molecular mechanisms in enhancing the sensitivity of multiple chemotherapeutic drugs, through targeting of mTOR, ERK/P70S6K, NF-κB/HIF-1 α, and Mitogen- Activated Protein Kinase (MAPK) signaling pathways, as well as by down-regulating the expression of CSC genes and Pyruvate Kinase isoenzyme M2 (PKM2). Through a comprehensive understanding of the molecular mechanisms of chemosensitization provided in this review, the rationale for the use of metformin in clinical combination medications can be more systematically and thoroughly explored for wider adoption against numerous cancer types.>.


Assuntos
Antineoplásicos/farmacologia , Metformina/farmacologia , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metformina/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Células-Tronco Neoplásicas , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...