Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matcha green tea (MGT) is a natural product that is currently used as a dietary supplement and may have significant anti-cancer properties. However, the molecular mechanism(s) underpinning its potential health benefits remain largely unknown. Here, we used MCF7 cells (an ER(+) human breast cancer cell line) as a model system, to systematically dissect the effects of MGT at the cellular level, via i) metabolic phenotyping and ii) unbiased proteomics analysis. Our results indicate that MGT is indeed sufficient to inhibit the propagation of breast cancer stem cells (CSCs), with an IC-50 of ~0.2 mg/ml, in tissue culture. Interestingly, metabolic phenotyping revealed that treatment with MGT is sufficient to suppress both oxidative mitochondrial metabolism (OXPHOS) and glycolytic flux, shifting cancer cells towards a more quiescent metabolic state. Unbiased label-free proteomics analysis identified the specific mitochondrial proteins and glycolytic enzymes that were down-regulated by MGT treatment. Moreover, to discover the underlying signalling pathways involved in this metabolic shift, we subjected our proteomics data sets to bio-informatics interrogation via Ingenuity Pathway Analysis (IPA) software. Our results indicate that MGT strongly affected mTOR signalling, specifically down-regulating many components of the 40S ribosome. This raises the intriguing possibility that MGT can be used as inhibitor of mTOR, instead of chemical compounds, such as rapamycin. In addition, other key pathways were affected, including the anti-oxidant response, cell cycle regulation, as well as interleukin signalling. Our results are consistent with the idea that MGT may have significant therapeutic potential, by mediating the metabolic reprogramming of cancer cells.
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PMID:Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways. 3015 55

Ribosome biogenesis is a fundamental cellular process and occurs mainly in the nucleolus in eukaryotes. The process is exceptionally complex and highly regulated by numerous ribosomal and non-ribosomal factors. A recent discovery strengthened the link between ribosome biogenesis and malignant transformation. Here, we determined that Nop-7-associated 2 (NSA2) is a nucleolar protein required for ribosome biogenesis. NSA2 knockdown reduced the rate of rRNA synthesis, diminishing the 60S ribosomal subunit. Moreover, we demonstrated that depletion of NSA2 suppressed protein synthesis. To investigate the signaling pathway affected by NSA2, NSA2 was depleted, which triggered the inactivation of the mTOR signaling pathway. Taken together, our findings reveal a novel function of NSA2 and provide insight into the regulation of ribosome biogenesis by NSA2.
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PMID:Nop-7-associated 2 (NSA2) is required for ribosome biogenesis and protein synthesis. 3024 19


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