Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

Young, Jung Han; Lee, Hojae

doi:10.15430/jcp.2016.21.4.209

Cited by 37 publications

(33 citation statements)

References 52 publications

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“…Transformed cells possess the capability of adjusting their metabolic demands toward the synthesis of macromolecules, mainly lipids for biogenesis of membranes and various signaling cues, in order to sustain their high proliferative rates . However, more unusual is their absolute dependency on de novo lipid synthesis, which thereby highlights an attractive metabolic addiction of the cancer cells . This metabolic predisposition might be exploited in multiple arenas for effective cancer therapeutics.…”

Section: Moving Forwardmentioning

confidence: 99%

Aberrant lipid metabolism in cancer cells – the role of oncolipid‐activated signaling

Ray

Roy

2017

The FEBS Journal

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Metabolic activity of malignant cells is very different from that of their nontransformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. In particular, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this for therapeutic benefit. Alterations in lipid metabolism are one of the main aspects of metabolic rewiring of transformed cells. Up-regulation of several lipogenic enzymes has been reported to be a characteristic of various cancer types. Lysophosphatidic acid (LPA), a simple byproduct of the lipid biosynthesis pathway, has gained immense importance due to its elevated level in several cancers and associated growth-promoting activity. Importantly, a current study revealed its role in increased de novo lipid synthesis through up-regulation of sterol regulatory element-binding protein 1, a master regulator of lipid metabolism. This review summarizes the recent insights in the field of oncolipid LPA-mediated signaling in regard to lipid metabolism in cancers. Future work in this domain is required to understand the up-regulation of the de novo synthesis pathway and the role of its end products in malignant cells. This will open a new arena of research toward the development of specific metabolic inhibitors that can add to the pre-existing chemotherapeutics in order to increase the efficacy of clinical output in cancer patients.

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Section: Moving Forwardmentioning

confidence: 99%

Aberrant lipid metabolism in cancer cells – the role of oncolipid‐activated signaling

Ray

Roy

2017

The FEBS Journal

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“…The cancer cells exploit lipid metabolic pathways in order to fulfil their demand for energy as well as biosynthetic precursors. Aberrations in lipid metabolism thus affects numerous cellular processes such as cell growth, proliferation, differentiation and cell survival 1 . Sphingolipids (SPLs), apart from the inceptive view of being considered as mere structural components, have evolved as crucial regulators of myriads of cellular functions.…”

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confidence: 99%

LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients

Bhadwal¹,

Dahiya²,

Shinde³

et al. 2020

Sci Rep

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perturbations in lipid metabolic pathways to meet the bioenergetic and biosynthetic requirements is a principal characteristic of cancer cells. Sphingolipids (SpLs) are the largest class of bioactive lipids associated to various aspects of tumorigenesis and have been extensively studied in cancer cell lines and experimental models. the clinical relevance of SpLs in human malignancies however is still poorly understood and needs further investigation. in the present study, we adopted a UHpLc-High resolution (orbitrap) Mass spectrometry (HRMS) approach to identify various sphingolipid species in breast cancer patients. A total of 49 SPLs falling into 6 subcategories have been identified. Further, integrating the multivariate analysis with metabolomics enabled us to identify an elevation in the levels of ceramide phosphates and sphingosine phosphates in tumor tissues as compared to adjacent normal tissues. the expression of genes involved in the synthesis of reported metabolites was also determined in local as well as TCGA cohort. A significant upregulation in the expression of CERK and SPHK1 was observed in tumor tissues in local and tcGA cohort. Sphingomyelin levels were found to be high in adjacent normal tissues. Consistent with the above findings, expression of SGMS1 in tumor tissues was downregulated in tcGA cohort only. clinical correlations of the selected metabolites and their performance as biomarkers was also evaluated. Significant ROC and positive correlation with Ki67 index highlight the diagnostic potential and clinical relevance of ceramide phosphates in breast cancer.Dysregulation of lipid homeostasis has become an established hallmark of cancer. The cancer cells exploit lipid metabolic pathways in order to fulfil their demand for energy as well as biosynthetic precursors. Aberrations in lipid metabolism thus affects numerous cellular processes such as cell growth, proliferation, differentiation and cell survival 1 . Sphingolipids (SPLs), apart from the inceptive view of being considered as mere structural components, have evolved as crucial regulators of myriads of cellular functions. The primary elements of sphingolipid metabolism such as ceramide, ceramide 1-phosphate and sphingosine 1-phosphate have recently emerged as key regulators in cancer cell growth, proliferation, survival, migration and drug resistance 2-4 . Numerous studies have described the elementary role of ceramide and sphingosine 1-phosphate rheostat in various types of cancers such as lung, breast and colon. However, these studies have provided the mechanistic details of sphingolipid metabolism in cancer cell lines and experimental models 5-7 , while their role in human malignancies is still poorly understood and needs further elucidation.Breast cancer continues to remain the most common malignancy among women worldwide 8 . The diagnosis rate of breast cancer among Indian females is as high as 25.8 per 100,000 women with a mortality rate of 12.7 per 100,000 women 9 . Despite advancement in diagnostic and therapeutic modalities, th...

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“…Observations have shown that rapid growth of cancer cells requires a sustainable supply of lipids for membrane formation. In view this, cancer cells have to enhance the uptake of lipids or activate de novo lipid synthesis which has been observed in many tumor types, including HCC . For instance, the observations showed high expressions of Fasn and Acly genes whose products are lipid metabolic pathway‐involved enzymes in cancer cells .…”

Section: Discussionmentioning

confidence: 95%

Integrated mRNA‐Seq and miRNA‐Seq analysis of PLCγ2‐overexpressing hepatocarcinoma cells and identification of the associated miRNA‐mRNA network

Chen

Zhu

Wei

et al. 2019

J of Cellular Biochemistry

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Our previous study has discovered the positive effect of phospholipase Cγ 2 (PLCγ2) on the growth of hepatocarcinoma cells; however, the underlying mechanism is far from being understood. For this reason, this study attempts to identify the differently expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in PLCγ2-overexpressing hepatocarcinoma cells. The results showed that totally 596 differently-expressed genes (DEGs) were identified in PLCγ2expressed cells, including 314 upregulated and 282 downregulated ones; according to gene ontology analysis, these DEGs were involved in different cellular processes. Concurrently, 34 differently-expressed miRNAs (DEMs) were also detected in PLCγ2-expressing hepatocarcinoma cells. Moreover, the integrative analysis of miRNA and mRNA expression profiles identified the potential regulatory network linked to hepatocarcinoma-related biological processes, including metabolic activity, gene expression, cell cycle, cell migration, and so on. To our knowledge, it is the first study on the effect of PLCγ2 on miRNA and mRNA expressions in hepatocarcinoma cells, and the findings provide new insights into the mechanism supporting the growthpromoting effect of PLCγ2 in hepatocarcinoma cells. K E Y W O R D S bioinformatic analysis, hepatocarcinoma cells, mRNA-miRNA network, phospholipase C gamma 2 F I G U R E 6 miRNA-mRNA negatively regulatory network in PLCγ2-overexpressing hepatocarcinoma cells. A, The miRNA-mRNA network related to PLCγ2-stimulated hepatocarcinoma cell growth by integrating the expression changes of target genes. B, The core of regulatory network. Red and green indicate upregulated and downregulated expressions, respectively. miRNA, microRNA; mRNA, messenger RNA; PLCγ2, positive effect of phospholipase Cγ 2

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Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

Cited by 37 publications

References 52 publications

Aberrant lipid metabolism in cancer cells – the role of oncolipid‐activated signaling

Aberrant lipid metabolism in cancer cells – the role of oncolipid‐activated signaling

LC-HRMS based approach to identify novel sphingolipid biomarkers in breast cancer patients

Integrated mRNA‐Seq and miRNA‐Seq analysis of PLCγ2‐overexpressing hepatocarcinoma cells and identification of the associated miRNA‐mRNA network

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