AMPK Regulation of Cell Growth, Apoptosis, Autophagy, and Bioenergetics

Paz, Marina Villanueva; Cotán, David; Garrido-Maraver, Juan; Oropesa-Ávila, Manuel; Mata, Mario de la; Delgado-Pavón, Ana; Lavera, Isabel de; Alcocer-Gómez, Elísabet; Álvarez-Córdoba, Mónica; Sánchez-Alcázar, José A.

doi:10.1007/978-3-319-43589-3_3

Cited by 68 publications

(62 citation statements)

References 119 publications

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“…SnRK1 can promote autophagy under abiotic stress in Arabidopsis ( Soto-Burgos and Bassham, 2017 ; Pu et al, 2017 ). In mammals, the SnRK1 orthologue, AMPK, can play a proapoptotic or pro-survival role depending on type of tissue and stress exposure, although the role of AMPK is highly complex and controversial during this process ( Villanueva-Paz et al, 2016 ). SnRK1 may play a similar role to AMPK, by maintaining CD balance to promote plant survival in plants overexpressing AFP2.…”

Section: Discussionmentioning

confidence: 99%

SnRK1α1 Antagonizes Cell Death Induced by Transient Overexpression of Arabidopsis thaliana ABI5 Binding Protein 2 (AFP2)

Carianopol

Gazzarrini

2020

Front. Plant Sci.

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Plants are continuously exposed to environmental stressors. They have thus evolved complex signaling pathways to govern responses to a variety of stimuli. The hormone abscisic acid (ABA) has been implicated in modulating both abiotic and biotic stress responses in plants. ABI5 Binding Proteins (AFPs) are a family of negative regulators of bZIP transcription factors of the AREB/ABF family, which promote ABA responses. AFP2 interacts with Snf1-Related protein Kinase 1 (SnRK1), which belongs to a highly conserved heterotrimeric kinase complex that is activated to re-establish energy homeostasis following stress. However, the role of this interaction is currently unknown. Here, we show that transient overexpression of Arabidopsis thaliana AFP2 in Nicotiana benthamiana leaves induces cell death (CD). Using truncated AFP2 constructs, we demonstrate that CD induction by AFP2 is dependent on the EAR domain. Co-expression of the catalytic subunit SnRK1α1, but not SnRK1α2, rescues AFP2-induced CD. Overexpression of SnRK1α1 has little effect on AFP2 protein level and does not affect AFP2 subcellular localization. Our results show that a high level of AFP2 is detrimental for cell function and that SnRK1α1 antagonizes AFP2-induced CD most likely through a mechanism that does not involve AFP2 protein degradation or a change in subcellular localization.

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Section: Discussionmentioning

confidence: 99%

SnRK1α1 Antagonizes Cell Death Induced by Transient Overexpression of Arabidopsis thaliana ABI5 Binding Protein 2 (AFP2)

Carianopol

Gazzarrini

2020

Front. Plant Sci.

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“…Accumulating evidence disclosed a strong relation between metabolism disturbances and the occurrence of vascular diseases, diabetes mellitus and cancer . 5′ AMP‐activated protein kinase enzyme, a highly conserved master regulator of metabolism, modulates several cellular functions implicated in cell fate including cell growth, apoptosis and autophagy . Fu et al .…”

Section: Discussionmentioning

confidence: 99%

A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Weng

Dokla

et al. 2018

Basic Clin Pharma Tox

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5' AMP-activated protein kinase enzyme (AMPK), a master regulator of cellular metabolism, is recognized for its association with various metabolic diseases, inflammation and cancer. In this study, we aimed to investigate the role of compound 59, an AMPK activator, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antiproliferative effects of compound 59 were assessed by MTT assays, flow cytometry, Western blotting, confocal microscopy and transmission electron microscopy. Relative to OSCC cells, normal human oral keratinocytes were almost insensitive to compound 59 treatment. Compound 59 induced apoptosis as indicated by caspase activation and PARP cleavage. In addition, it inhibited JAK/STAT3 signalling, arrested cells in the G1 phase, increased reactive oxygen species (ROS) generation and promoted autophagy. Interestingly, pre-treatment with a protein tyrosine phosphatase (PP2A) inhibitor, cantharidin, partially reversed compound 59-induced down-regulation of p-JAK2 and p-STAT3, thereby suggesting the involvement of a protein tyrosine phosphatase. Together, these findings substantiate the potential of compound 59 for the treatment of OSCC patients.

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“…24 As a major metabolic regulator, AMPK is activated in numerous types of cancer cells under excessive stress and contributes to cell apoptosis and death. 25 Multiple studies indicated AMPK contains redox-sensitive cysteines that are rapidly oxidized during oxidative stress and could inhibit glycolysis. [26][27][28] We hypothesized that TAM might activate AMPK signalling in GBC through a redoxdependent mechanism.…”

Section: Tam Suppresses Glycolysis By Activating Ampk Signalling Inmentioning

confidence: 99%

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

Huang

Wang

Chen

et al. 2019

J Cellular Molecular Medi

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Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females two-threefold higher than males, suggesting oestrogen/oestrogen receptors (ERs) signalling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Quantitative real-time PCR was used to investigate mRNA levels. Protein expression was measured by immunohistochemistry and Western blot. Glycolytic levels were measured by glucose consumption and lactic acid measurement. The antitumour activity of TAM alone or with cisplatin was examined with CCK8 assay, colony formation, flow cytometry and in vivo models. The results revealed that ERɑ expression was higher in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor Nrf2 expression and its target genes, leading to the activation of AMPK, which subsequently induced impaired glycolysis and survival advantages. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of oestrogens by ovariectomy in nude mice prevented CDDP resistance. In summary, these results provide basis for TAM treatment for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC.

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AMPK Regulation of Cell Growth, Apoptosis, Autophagy, and Bioenergetics

Cited by 68 publications

References 119 publications

SnRK1α1 Antagonizes Cell Death Induced by Transient Overexpression of Arabidopsis thaliana ABI5 Binding Protein 2 (AFP2)

SnRK1α1 Antagonizes Cell Death Induced by Transient Overexpression of Arabidopsis thaliana ABI5 Binding Protein 2 (AFP2)

A 5′ AMP‐Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma

Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer

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