p53 as a Regulator of Lipid Metabolism in Cancer

Parrales, Alejandro; Iwakuma, Tomoo

doi:10.3390/ijms17122074

Cited by 83 publications

(69 citation statements)

References 80 publications

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“…Conflicting results exist in the literature regarding the PgR status of CAMA-1 which is reported to be positive or negative in different studies. Furthermore, the TP53 status is different for the three luminal cell lines with T-47D expressing mutated protein [6,27] and TP53 is known to regulate lipid metabolism in cancer [42]. This indicates within-group differences in the lipidome of cells representing the luminal subtype and suggests that CAMA-1 should not necessarily be classified as the same luminal subtype as MCF7 and T-47D.…”

Section: Plos Onementioning

confidence: 96%

Lipidomic study of cell lines reveals differences between breast cancer subtypes

et al. 2020

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Breast cancer (BC) is the most prevalent type of cancer in women in western countries. BC mortality has not declined despite early detection by screening, indicating the need for better informed treatment decisions. Therefore, a novel noninvasive diagnostic tool for BC would give the opportunity of subtype-specific treatment and improved prospects for the patients. Heterogeneity of BC tumor subtypes is reflected in the expression levels of enzymes in lipid metabolism. The aim of the study was to investigate whether the subtype defined by the transcriptome is reflected in the lipidome of BC cell lines. A liquid chromatography mass spectrometry (LC-MS) platform was applied to analyze the lipidome of six cell lines derived from human BC cell lines representing different BC subtypes. We identified an increased abundance of triacylglycerols (TG) � C-48 with moderate or multiple unsaturation in fatty acyl chains and down-regulated ether-phosphatidylethanolamines (PE) (C-34 to C-38) in cell lines representing estrogen receptor and progesterone receptor positive tumor subtypes. In a cell line representing HER2-overexpressing tumor subtype an elevated expression of TG (� C-46), phosphatidylcholines (PC) and PE containing short-chained (� C-16) saturated or monounsaturated fatty acids were observed. Increased abundance of PC � C-40 was found in cell lines of triple negative BC subtype. In addition, differences were detected in lipidomes within these previously defined subtypes. We conclude that subtypes defined by the transcriptome are indeed reflected in differences in the lipidome and, furthermore, potentially biologically relevant differences may exist within these defined subtypes.

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Section: Plos Onementioning

confidence: 96%

Lipidomic study of cell lines reveals differences between breast cancer subtypes

et al. 2020

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“…At the same time, wild-type (WT) p53 upregulates fatty acid oxidation by elevating expression of lipin 1 and guanidinoacetate methyltransferase (Liu, Zhang, Hu, & Feng, 2015). Moreover, via direct transcriptional control of such targets as sterol-regulatory-binding protein-1 (SREBP-1), acetyl-CoA dehydrogenase family member 11 (ACAD11), LIPIN1, malonyl-CoA decarboxylase (MCD), dehydrogenase/reductase 3 (DHRS3), carnitine palmitoyltransferase 1C (CPT1C) and caveolin 1, p53 controls multiple nodes in lipid metabolism (Parrales & Iwakuma, 2016). …”

Section: P53 As a Metabolic Regulatormentioning

confidence: 99%

Ceramide Signaling and p53 Pathways

Jeffries¹,

Krupenko

2018

Advances in Cancer Research

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Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance. This regulation, however, can be pro-death or pro-survival depending on cancer type, the balance between ceramide species, the rate of their synthesis and utilization, and the availability of a specific array of downstream targets. This chapter highlights the central role of ceramide in sphingolipid metabolism, its role in cancer, specific effectors in ceramide pathways controlled by p53, and coregulation of ceramide and p53 signaling. We discuss the recent studies, which underscore the function of p53 in the regulation of ceramide pathways and the reciprocal regulation of p53 by ceramide. This complex relationship is based on several molecular mechanisms including the p53-dependent transcriptional regulation of enzymes in sphingolipid pathways, the activation of mutant p53 through ceramide-mediated alternative splicing, as well as modulation of the p53 function through direct and indirect effects on p53 coregulators and downstream targets. Further insight into the connections between ceramide and p53 will allow simultaneous targeting of the two pathways with a potential to yield more efficient anticancer therapeutics.

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“…In particular, tumor cells exhibit an increased glucose uptake, glycolysis, lactate production, glutamine consumption, nucleic acid metabolism, and lipid and cholesterol synthesis [90,101,102]. …”

Section: P53 and Mutant P53 Protein Functionsmentioning

confidence: 99%

Mutant p53 Protein and the Hippo Transducers YAP and TAZ: A Critical Oncogenic Node in Human Cancers

Ferraiuolo¹,

Blandino²,

Strano³

2017

IJMS

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p53 protein is a well-known tumor suppressor factor that regulates cellular homeostasis. As it has several and key functions exerted, p53 is known as “the guardian of the genome” and either loss of function or gain of function mutations in the TP53 coding protein sequence are involved in cancer onset and progression. The Hippo pathway is a key regulator of developmental and regenerative physiological processes but if deregulated can induce cell transformation and cancer progression. The p53 and Hippo pathways exert a plethora of fine-tuned functions that can apparently be in contrast with each other. In this review, we propose that the p53 status can affect the Hippo pathway function by switching its outputs from tumor suppressor to oncogenic activities. In detail, we discuss: (a) the oncogenic role of the protein complex mutant p53/YAP; (b) TAZ oncogenic activation mediated by mutant p53; (c) the therapeutic potential of targeting mutant p53 to impair YAP and TAZ oncogenic functions in human cancers.

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p53 as a Regulator of Lipid Metabolism in Cancer

Cited by 83 publications

References 80 publications

Lipidomic study of cell lines reveals differences between breast cancer subtypes

Lipidomic study of cell lines reveals differences between breast cancer subtypes

Ceramide Signaling and p53 Pathways

Mutant p53 Protein and the Hippo Transducers YAP and TAZ: A Critical Oncogenic Node in Human Cancers

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