New links between lipid accumulation and cancer progression

Nickels, Jr. Joseph T.

doi:10.1074/jbc.h118.002654

Cited by 30 publications

(24 citation statements)

References 9 publications

(14 reference statements)

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“…Furthermore, both AMPK and Akt are the upstream regulator of sterol regulatory element-binding protein-1 (SREBP-1) and can directly phosphorylate SREBP-1. Recently, SREBP-1, which gets upregulated in different types of cancer, has been linked to play a role in the oncogenic signaling-mediated glucose uptake and de novo lipogenesis [46][47][48]. The pharmacological targeting of SREBP-1 has revealed to significantly inhibit the glioblastoma cell growth, suggesting it as a novel molecular target in cancer [49].…”

Section: Discussionmentioning

confidence: 99%

Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway

2021

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Background Metabolic dysregulation is one of the hallmarks of tumor cell proliferation. Evidence indicates the potential role of the 5′adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B/Akt signaling pathway in regulating cell proliferation, survival, and apoptosis. The present study explores the effect of metformin HCl and the combination of α- and β-asarone on the proliferation of HepG2 cells in the presence of high glucose levels simulating the diabetic-hepatocellular carcinoma (HCC) condition. Results The metformin and asarone reduced HepG2 cell viability in a dose-dependent manner and induced morphological changes as indicated by methyl thiazolyl tetrazolium (MTT) assay. The metformin and asarone arrested the cells at the G0/G1 phase, upregulated the expression of AMPK, and downregulated Akt expression in high glucose conditions as identified by the flow cytometry technique. Further, the upregulated AMPK led to a decrease in the expression of phosphoenolpyruvate carboxykinase-2 (PCK-2) and sterol regulatory element-binding protein-1 (SREBP-1). Conclusion The anti-proliferative effect of metformin and asarone in the diabetic-HCC condition is mediated via AMPK and Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway

2021

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“…Recently Zhao et al used a xenograft in a murine model to show that PKM2 is able to activate the nuclear transcription factor SREBP-1a, leading to cell proliferation and increased tumor progression. The interaction appears to be highly specific for this type of SREBP-1a (91, 92). This is an important result as it confirms the role of lipid accumulation in cancer progression.…”

Section: Metabolism Of Cancer Cells and Thyroid Hormones: Pkm2mentioning

confidence: 98%

The Role of Thyroid Hormones in Hepatocyte Proliferation and Liver Cancer

et al. 2019

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Thyroid hormones T3 and T4 (thyroxine) control a wide variety of effects related to development, differentiation, growth and metabolism, through their interaction with nuclear receptors. But thyroid hormones also produce non-genomic effects that typically start at the plasma membrane and are mediated mainly by integrin αvβ3, although other receptors such as TRα and TRβ are also able to elicit non-genomic responses. In the liver, the effects of thyroid hormones appear to be particularly important. The liver is able to regenerate, but it is subject to pathologies that may lead to cancer, such as fibrosis, cirrhosis, and non-alcoholic fatty liver disease. In addition, cancer cells undergo a reprogramming of their metabolism, resulting in drastic changes such as aerobic glycolysis instead of oxidative phosphorylation. As a consequence, the pyruvate kinase isoform M2, the rate-limiting enzyme of glycolysis, is dysregulated, and this is considered an important factor in tumorigenesis. Redox equilibrium is also important, in fact cancer cells give rise to the production of more reactive oxygen species (ROS) than normal cells. This increase may favor the survival and propagation of cancer cells. We evaluate the possible mechanisms involving the plasma membrane receptor integrin αvβ3 that may lead to cancer progression. Studying diseases that affect the liver and their experimental models may help to unravel the cellular pathways mediated by integrin αvβ3 that can lead to liver cancer. Inhibitors of integrin αvβ3 might represent a future therapeutic tool against liver cancer. We also include information on the possible role of exosomes in liver cancer, as well as on recent strategies such as organoids and spheroids, which may provide a new tool for research, drug discovery, and personalized medicine.

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“…Upon cholesterol depletion, the SCAP-SREBP complex moves to the trans-Golgi, where SREBPs are cleaved by the proteases S1P and S2P to allow for SREBP translocation from the Golgi complex to the nucleus, where they regulate the expression of lipogenesis-inducing genes and transporters. 151,152 Studies have shown important roles for SREBP function in T cells. Deletion of SCAP in T cells does not affect homeostatic proliferation, but impairs activation-induced cell growth, proliferation and differentiation, which promotes clearance of viral infections in vivo.…”

Section: Lipid and Cholesterol Synthesismentioning

confidence: 99%

Signaling networks in immunometabolism

Saravia¹,

Raynor²,

Chapman³

et al. 2020

Cell Res

155

136

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Adaptive immunity is essential for pathogen and tumor eradication, but may also trigger uncontrolled or pathological inflammation. T cell receptor, co-stimulatory and cytokine signals coordinately dictate specific signaling networks that trigger the activation and functional programming of T cells. In addition, cellular metabolism promotes T cell responses and is dynamically regulated through the interplay of serine/threonine kinases, immunological cues and nutrient signaling networks. In this review, we summarize the upstream regulators and signaling effectors of key serine/threonine kinase-mediated signaling networks, including PI3K-AGC kinases, mTOR and LKB1-AMPK pathways that regulate metabolism, especially in T cells. We also provide our perspectives about the pending questions and clinical applicability of immunometabolic signaling. Understanding the regulators and effectors of immunometabolic signaling networks may uncover therapeutic targets to modulate metabolic programming and T cell responses in human disease.

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New links between lipid accumulation and cancer progression

Cited by 30 publications

References 9 publications

Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway

Metformin and asarone inhibit HepG2 cell proliferation in a high glucose environment by regulating AMPK and Akt signaling pathway

The Role of Thyroid Hormones in Hepatocyte Proliferation and Liver Cancer

Signaling networks in immunometabolism

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