Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles

Bruno, Paola; Calastretti, Angela; Priulla, Marcella; Asnaghi, Laura; Scarlatti, Francesca; Nicolin, A; Canti, Gianfranco

doi:10.1016/j.cellsig.2007.06.008

Cited by 19 publications

(11 citation statements)

References 45 publications

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“…8b-d). Autophagy was induced by starvation of cells cultured in serum free Earle's Balanced Salt Solution (EBSS) medium for 2 h and 4 h, as previously reported [47–49]. The lysosome inhibitor bafilomycin A1 was added to the medium of 4 h starved cells as a positive control to estimate maximal APP-CTF accumulation.…”

Section: Resultsmentioning

confidence: 99%

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

Guix

Sannerud

Berditchevski

et al. 2017

Mol Neurodegeneration

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BackgroundThe mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer’s disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase.MethodsWe searched for tetraspanins with altered expression in AD brains. The function of the selected tetraspanin was studied in vitro and the physiological relevance of our findings was confirmed in vivo.ResultsTetraspanin-6 (TSPAN6) is increased in AD brains and overexpression in cells exerts paradoxical effects on Amyloid Precursor Protein (APP) metabolism, increasing APP-C-terminal fragments (APP-CTF) and Aβ levels at the same time. TSPAN6 affects autophagosome-lysosomal fusion slowing down the degradation of APP-CTF. TSPAN6 recruits also the cytosolic, exosome-forming adaptor syntenin which increases secretion of exosomes that contain APP-CTF.ConclusionsTSPAN6 is a key player in the bifurcation between lysosomal-dependent degradation and exosome mediated secretion of APP-CTF. This corroborates the central role of the autophagosomal/lysosomal pathway in APP metabolism and shows that TSPAN6 is a crucial player in APP-CTF turnover.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-017-0165-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

Guix

Sannerud

Berditchevski

et al. 2017

Mol Neurodegeneration

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“…Conversely, in the absence of metabolic stress, cells most rely on AKT/p70S6K pathway for cell motility. Interestingly, it has been shown that cells expressing constitutively active AKT are highly sensitized to cell death induced by nutrient and growth factor deprivation [26]. In this view, TRAP1 expression could represent a mechanism of resistance adopted by cancer cells when nutrient scarcity requires downregulation of the AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways

Agliarulo

Matassa

Amoroso

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cell motility is a highly dynamic phenomenon that is essential to physiological processes such as morphogenesis, wound healing and immune response, but also involved in pathological conditions such as metastatic dissemination of cancers. The involvement of the molecular chaperone TRAP1 in the regulation of cell motility, although still controversial, has been recently investigated along with some well-characterized roles in cancer cell survival and drug resistance in several tumour types. Among different functions, TRAP1-dependent regulation of protein synthesis seems to be involved in the migratory behaviour of cancer cells and, interestingly, the expression of p70S6K, a kinase responsible for translation initiation, playing a role in cell motility, is regulated by TRAP1. In this study, we demonstrate that TRAP1 silencing enhances cell motility in vitro but compromises the ability of cells to overcome stress conditions, and that this effect is mediated by the AKT/p70S6K pathway. In fact: i) inhibition of p70S6K activity specifically reduces migration in TRAP1 knock-down cells; ii) nutrient deprivation affects p70S6K activity thereby impairing cell migration only in TRAP1-deficient cells; iii) TRAP1 regulates the expression of both AKT and p70S6K at post-transcriptional level; and iii) TRAP1 silencing modulates the expression of genes involved in cell motility and epithelial-mesenchymal transition. Notably, a correlation between TRAP1 and AKT expression is found in vivo in human colorectal tumours. These results provide new insights into TRAP1 role in the regulation of cell migration in cancer cells, tumour progression and metastatic mechanisms.

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“…Excessive self-digestion and degradation of essential cellular components by autophagy promote cell death; however, autophagy might also promote cell survival by generating free amino acids and fatty acids required to maintain function during nutrient-limiting conditions [45]. In addition to the great number of extracellular (e.g.…”

Section: Effects Of Oxidized Extracellular Ehcyss On Proinflammatmentioning

confidence: 99%

Cysteine/cystine redox signaling in cardiovascular disease

Jones

2011

Free Radical Biology and Medicine

372

232

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Extracellular thiol/disulfide redox environments are highly regulated in healthy individuals. The major thiol/disulfide redox couple in human plasma is cysteine (Cys) and its disulfide form, cystine (CySS). Oxidation of this redox couple measured as a more positive steady-state redox potential (Eh) is associated with risk factors for cardiovascular disease (CVD), including aging, smoking, obesity, and alcohol abuse. Rodent and vascular cell studies show that extracellular redox state of Cys/CySS (EhCySS) can play a vital role in controlling CVD through proinflammatory signaling. This inflammatory signaling is regulated by cell surface protein redox state and involves mitochondrial oxidation, nuclear factor-κB activation, and elevated expression of genes for monocyte recruitment to endothelial cells. Gene array and proteomics studies reveal the global nature of redox effects, and different cell types, e.g., endothelial cells, monocytes, fibroblasts, and epithelial cells, show cell-specific redox responses with different phenotypic traits, e.g., proliferation and apoptosis, which can contribute to CVD. The critical nature of the proinflammatory redox signaling and cell biology associated with EhCySS supports the use of plasma levels of Cys, CySS, and EhCySS as key indicators of vascular health. Plasma redox state-based pharmacologic interventions to control or improve EhCySS may be effective in preventing CVD onset or progression.

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Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles

Cited by 19 publications

References 45 publications

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways

Cysteine/cystine redox signaling in cardiovascular disease

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