Abstract：
:The conserved serine/threonine kinase mTOR (the mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway, forms two distinct multiprotein complexes: mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin, activates S6K1 and 4EBP1, which are involved in mRNA translation. It is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals, and essential signalling pathways, such as PI3K, MAPK and AMPK, in order to control cell growth, proliferation and survival. mTORC2 is considered resistant to rapamycin and is generally insensitive to nutrients and energy signals. It activates PKC-α and AKT and regulates the actin cytoskeleton. Deregulation of multiple elements of the mTOR pathway (PI3K amplification/mutation, PTEN loss of function, AKT overexpression, and S6K1, 4EBP1 and eIF4E overexpression) has been reported in many types of cancers, particularly in melanoma, where alterations in major components of the mTOR pathway were reported to have significant effects on tumour progression. Therefore, mTOR is an appealing therapeutic target and mTOR inhibitors, including the rapamycin analogues deforolimus, everolimus and temsirolimus, are submitted to clinical trials for treating multiple cancers, alone or in combination with inhibitors of other pathways. Importantly, temsirolimus and everolimus were recently approved by the FDA for the treatment of renal cell carcinoma, PNET and giant cell astrocytoma. Small molecules that inhibit mTOR kinase activity and dual PI3K-mTOR inhibitors are also being developed. In this review, we aim to survey relevant research, the molecular mechanisms of signalling, including upstream activation and downstream effectors, and the role of mTOR in cancer, mainly in melanoma.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Pópulo H,Lopes JM,Soares Pdoi
10.3390/ijms13021886subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1886-918issue
2issn
1422-0067pii
ijms-13-01886journal_volume
13pub_type
杂志文章,评审abstract：:Melatonin (MT; N-acetyl-5-methoxytryptamine) is a pleiotropic signaling molecule that has been demonstrated to play an important role in plant growth, development, and regulation of environmental stress responses. Studies have been conducted on the role of the exogenous application of MT in a few species, but the pote...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20051176
更新日期：2019-03-07 00:00:00
abstract：:Geopropolis is a resin mixed with mud, produced only by stingless bees. Despite being popularly known for its medicinal properties, few scientific studies have proven its biological activities. In this context, the objective of this study was to determine the chemical composition and antioxidant, anti-inflammatory, an...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18050953
更新日期：2017-05-03 00:00:00
abstract：:Chaetomium globosum is frequently isolated in water-damaged buildings and produces two mycotoxins called chaetoglobosins A and C when cultured on building material. In this study, the influence of ambient pH on the growth of C. globosum was examined on an artificial medium. This fungus was capable of growth on potato ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms9122357
更新日期：2008-12-01 00:00:00
abstract：:Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19030808
更新日期：2018-03-11 00:00:00
abstract：:Cardiovascular disease (CVD) is the main cause of death globally and responsible for the second highest number of deaths in Canada. Medical advancements in the treatment of CVD have led to patients living longer with CVD but often progressing to another condition called heart failure (HF). As a result, HF has emerged ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,meta分析,评审
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更新日期：2019-02-19 00:00:00
abstract：:The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-11-22 00:00:00
abstract：:(1) Background: In a previous study, we found that two phenotypes related to platelet reactivity, measured with the PFA-100 system, were highly heritable. The aim of the present study was to identify genetic determinants that influence the variability of these phenotypes: closure time of collagen-ADP (Col-ADP) and of ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2019-06-30 00:00:00
abstract：:Cysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2019-07-23 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms17091428
更新日期：2016-08-31 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2020-05-23 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2017-07-06 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2016-04-19 00:00:00
abstract：:Molecular motors are microtubule-based proteins which contribute to many cell functions, such as intracellular transportation and cell division. The details of the nature of the mutual interactions between motors and microtubules still needs to be extensively explored. However, electrostatic interaction is known as on...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21144935
更新日期：2020-07-13 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19103104
更新日期：2018-10-10 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21176065
更新日期：2020-08-23 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21020371
更新日期：2020-01-07 00:00:00
abstract：:The consumption of polyphenols has frequently been associated with low incidence of degenerative diseases. Most of these natural antioxidants come from fruits, vegetables, spices, grains and herbs. For this reason, there has been increasing interest in identifying plant extract compounds. Polymeric tannins and monomer...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms151120382
更新日期：2014-11-06 00:00:00
abstract：:The interactions of chemokines with their G protein-coupled receptors promote the migration of leukocytes during normal immune function and as a key aspect of the inflammatory response to tissue injury or infection. This review summarizes the major cellular and biochemical mechanisms by which the interactions of chemo...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
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更新日期：2017-02-07 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms12128539
更新日期：2011-01-01 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2017-11-24 00:00:00
abstract：:3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important, multi-functional oncogenic...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2020-06-30 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13044920
更新日期：2012-01-01 00:00:00
abstract：:The tumor-suppressor protein p16 is paradoxically overexpressed in cervical cancer (CC). Despite its potential as a biomarker, its clinical value and the reasons for its failure in tumor suppression remain unclear. Our purpose was to determine p16 clinical and biological significance in CC. p16 expression pattern was ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21062125
更新日期：2020-03-19 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms140612520
更新日期：2013-06-14 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21155224
更新日期：2020-07-23 00:00:00
abstract：:The Dunkin Hartley (DH) guinea pig is a widely used naturally occurring osteoarthritis model. The aim of this study was to provide detailed evidence of age-related changes in articular cartilage, subchondral bone mineral density, and estradiol levels. We studied the female Dunkin Hartley guinea pigs at 1, 3, 6, 9, and...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
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更新日期：2014-08-05 00:00:00
abstract：:Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a serious pest in the sericulture industry, which has caused damage and losses in recent years. With the widespread use of insecticides, the insecticide resistance of G. pyloalis has becomes increasingly apparent. In order to find other effective methods to contr...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21051904
更新日期：2020-03-10 00:00:00
abstract：:The activation of extracellular signal-regulated kinases (ERK) leads to a number of cellular changes associated with the development of long-term memory. Using cultured cortical neurons, we previously showed that the n-hexane extract prepared from the peels of Citrus grandis (Kawachi bankan) induces the activation of ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13055338
更新日期：2012-01-01 00:00:00
abstract：:The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual substrates are degraded during selective autophagy in response to bo...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21020578
更新日期：2020-01-16 00:00:00
abstract：:Plants have evolved strategies to tightly regulate metabolism during acclimation to a changing environment. Low temperature significantly constrains distribution, growth and yield of many temperate plant species. Exposing plants to low but non-freezing temperature induces a multigenic processes termed cold acclimation...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20215411
更新日期：2019-10-30 00:00:00
