mTOR and Tumor Cachexia

Duval, Adrian Paul; Jeanneret, Cheryl; Santoro, Tania; Dormond, Olivier

doi:10.3390/ijms19082225

Cited by 27 publications

(23 citation statements)

References 146 publications

(181 reference statements)

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“…Low serum concentrations of IGF-1 are present in cachectic patients, while there seems to be a peripheral GH and Insulin resistance, which leads to a negative amino acid balance in skeletal muscle. The therapeutic use, though, of Insulin, GH, or IGF-1 is currently not recommended due to massive side effects [83]. GH/IGF-1 provides an anti-apopototic environment that could eventually accelerate the development of cancer [84,85].…”

Section: Hormonesmentioning

confidence: 99%

Pancreatic Cancer and Cachexia—Metabolic Mechanisms and Novel Insights

et al. 2020

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Cachexia is a major characteristic of multiple non-malignant diseases, advanced and metastatic cancers and it is highly prevalent in pancreatic cancer, affecting almost 70%–80% of the patients. Cancer cachexia is a multifactorial condition accompanied by compromised appetite and changes in body composition, i.e., loss of fat. It is associated with lower effectiveness of treatment, compromised quality of life, and higher mortality. Understanding the complex pathways underlying the pathophysiology of cancer cachexia, new therapeutic targets will be unraveled. The interplay between tumor and host factors, such as cytokines, holds a central role in cachexia pathophysiology. Cytokines are possibly responsible for anorexia, hypermetabolism, muscle proteolysis, and apoptosis. In particular, cachexia in pancreatic cancer might be the result of the surgical removal of pancreas parts. In recent years, many studies have been carried out to identify an effective treatment algorithm for cachexia. Choosing the most appropriate treatment, the clinical effect and the risk of adverse effects should be taken under consideration. The purpose of this review is to highlight the pathophysiological mechanisms as well as the current ways of cachexia treatment in the pharmaceutical and the nutrition field.

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Section: Hormonesmentioning

confidence: 99%

Pancreatic Cancer and Cachexia—Metabolic Mechanisms and Novel Insights

et al. 2020

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“…Furthermore, a member of the ubiquitin-proteasome pathway (MuRF1) pivotal to muscle wasting in tumor-bearing mice (and other murine models of muscle wasting) is critical for maintenance of the NMJ (17). Additionally, recent mouse studies of mTOR signaling, a key regulator of protein synthesis that is suppressed by inflammatory mediators in cancer cachexia (18), have shown that muscle-specific deletion of mTOR or Raptor results in muscle fibrillation and NMJ fragmentation (19).…”

Section: Introductionmentioning

confidence: 99%

Neuromuscular junctions are stable in patients with cancer cachexia

Boehm¹,

Miller²,

Wishart³

et al. 2020

Journal of Clinical Investigation

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“…Inhibition by Gln was below 50%, pointing to much lower affinity of SLC7A5 for glutamine (Napolitano et al, 2015). Amino acids, including leucine and glutamine, are necessary for cell growth and proliferation, processes augmented in cancer cells and controlled by mechanistic target of rapamycin (mTOR) regulating cell growth, what leads to protein translation and macrophagy inhibition (Nicklin et al, 2009;Efeyan et al, 2015;Duval et al, 2018). SLC7A11 (xCT) catalyzes uptake of cystine in an exchange with glutamate and, through formation of cysteine, increases the level of glutathione in the cell, protecting the cell from oxidative stress (Lewerenz et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Amino Acid Transporter SLC6A14 (ATB0,+) – A Target in Combined Anti-cancer Therapy

Nałęcz

2020

Front. Cell Dev. Biol.

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Cancer cells are characterized by quick growth and proliferation, demanding constant supply of various nutrients. Several plasma membrane transporters delivering such compounds are upregulated in cancer. Solute carrier family 6 member 14 (SLC6A14), known as amino acid transporter B 0,+ (ATB 0,+) transports all amino acids with exception of the acidic ones: aspartate and glutamate. Its malfunctioning is correlated with several pathological states and it is upregulated in solid tumors. The high expression of SLC6A14 is prognostic and unfavorable in pancreatic cancer, while in breast cancer it is expressed in estrogen receptor positive cells. As many plasma membrane transporters it resides in endoplasmic reticulum (ER) membrane after translation before further trafficking through Golgi to the cell surface. Transporter exit from ER is strictly controlled. The proper folding of SLC6A14 was shown to be controlled from the cytoplasmic side by heat shock proteins, further exit from ER and formation of coatomer II (COPII) coated vesicles depends on specific interaction with COPII cargo-recognizing subunit SEC24C, phosphorylated by kinase AKT. Inhibition of heat shock proteins, known to be upregulated in cancer, directs SLC6A14 to degradation. Targeting proteins regulating SLC6A14 trafficking is proposed as an additional pharmacological treatment of cancer.

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mTOR and Tumor Cachexia

Cited by 27 publications

References 146 publications

Pancreatic Cancer and Cachexia—Metabolic Mechanisms and Novel Insights

Pancreatic Cancer and Cachexia—Metabolic Mechanisms and Novel Insights

Neuromuscular junctions are stable in patients with cancer cachexia

Amino Acid Transporter SLC6A14 (ATB0,+) – A Target in Combined Anti-cancer Therapy

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