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1.
Drug Discov Today ; 29(5): 103980, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614160

RESUMO

Fatty acid binding protein 7 (FABP7) is an intracellular protein involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). FABP7 is upregulated up to 20-fold in multiple cancers, usually correlated with poor prognosis. FABP7 silencing or pharmacological inhibition suggest FABP7 promotes cell growth, migration, invasion, colony and spheroid formation/increased size, lipid uptake, and lipid droplet formation. Xenograft studies show that suppression of FABP7 inhibits tumour formation and tumour growth, and improves host survival. The molecular mechanisms involve promotion of FA uptake, lipid droplets, signalling [focal adhesion kinase (FAK), proto-oncogene tyrosine-protein kinase Src (Src), mitogen-activated protein kinase kinase/p-extracellular signal-regulated kinase (MEK/ERK), and Wnt/ß-catenin], hypoxia-inducible factor 1-alpha (Hif1α), vascular endothelial growth factor A/prolyl 4-hydroxylase subunit alpha-1 (VEGFA/P4HA1), snail family zinc finger 1 (Snail1), and twist-related protein 1 (Twist1). The oncogenic capacity of FABP7 makes it a promising pharmacological target for future cancer treatments.


Assuntos
Proteína 7 de Ligação a Ácidos Graxos , Neoplasias , Animais , Humanos , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Supressoras de Tumor
2.
Drug Discov Today ; 28(7): 103628, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230284

RESUMO

Fatty acid binding protein 5 (FABP5, or epidermal FABP) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. In patient-derived tumours, FABP5 expression is increased up to tenfold, often co-expressed with other cancer-related proteins. High tumoral FABP5 expression is associated with poor prognosis. FABP5 activates transcription factors (TFs) leading to increased expression of proteins involved in tumorigenesis. Genetic and pharmacological preclinical studies show that inhibiting FABP5 reduces protumoral markers, whereas elevation of FABP5 promotes tumour growth and spread. Thus, FABP5 might be a valid target for novel therapeutics. The evidence base is currently strongest for liver, prostate, breast, and brain cancers, and squamous cell carcinoma (SCC), which could represent relevant patient populations for any drug discovery programme.


Assuntos
Neoplasias , Masculino , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Ácidos Graxos/metabolismo , Proliferação de Células , Fígado/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo
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