The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth

Gouw, Arvin M.; Margulis, Katherine; Liu, Natalie S.; Raman, Sudha Janaki; Mancuso, Anthony A.; Toal, Georgia G.; Ling, Taotao; Mosley, Adriane; Hsieh, Annie L.; Sullivan, Delaney K.; Stine, Zachary E.; Altman, Brian J.; Schulze, Almut; Dang, Chi V.; Zare, Richard N.; Felsher, Dean W.

doi:10.1016/j.cmet.2019.07.012

Cited by 135 publications

(128 citation statements)

References 113 publications

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“…3). 33,58 MYC also regulates fatty acid synthesis through interactions with discrete master regulators. MondoA is a nutrient-sensing transcription factor.…”

Section: Myc Regulation Of Lipid Metabolismmentioning

confidence: 99%

“…59 MYC also induces the sterol-response element-binding protein 1 (SREBP1) expression, and acts in conjunction with SREBP1 to synergistically activate the transcription of fatty acid synthesis genes. 58 In addition to fatty acids, MYC effectively reprograms cholesterol metabolism by upregulation of 3-hydroxy-3-methyl-glutarylcoenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis during malignant transformation. 60 Moreover, it appeared that HMGCR is necessary for MYC Fig.…”

Section: Myc Regulation Of Lipid Metabolismmentioning

confidence: 99%

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Regulation of cancer cell metabolism: oncogenic MYC in the driver’s seat

Dong

Liu

et al. 2020

Sig Transduct Target Ther

230

169

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Cancer cells must rewire cellular metabolism to satisfy the demands of unbridled growth and proliferation. As such, most human cancers differ from normal counterpart tissues by a plethora of energetic and metabolic reprogramming. Transcription factors of the MYC family are deregulated in up to 70% of all human cancers through a variety of mechanisms. Oncogenic levels of MYC regulates almost every aspect of cellular metabolism, a recently revisited hallmark of cancer development. Meanwhile, unrestrained growth in response to oncogenic MYC expression creates dependency on MYC-driven metabolic pathways, which in principle provides novel targets for development of effective cancer therapeutics. In the current review, we summarize the significant progress made toward understanding how MYC deregulation fuels metabolic rewiring in malignant transformation.

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“…3). 33,58 MYC also regulates fatty acid synthesis through interactions with discrete master regulators. MondoA is a nutrient-sensing transcription factor.…”

Section: Myc Regulation Of Lipid Metabolismmentioning

confidence: 99%

Section: Myc Regulation Of Lipid Metabolismmentioning

confidence: 99%

Regulation of cancer cell metabolism: oncogenic MYC in the driver’s seat

Dong

Liu

et al. 2020

Sig Transduct Target Ther

230

169

View full text Add to dashboard Cite

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“…Both MYC (Yue et al, 2017) and HIF-2α (Elorza et al, 2012) activate the expression of the amino acid transporter SLC7A5 to promote essential amino acid (EAA) uptake. Both MYC (Gouw et al, 2019;Casciano et al, 2020) and HIF-2α (Rankin et al, 2009;Qiu et al, 2015) regulate lipid metabolism.…”

Section: Myc and Hif Cooperate To Reprogram Cancer Cell Metabolism Anmentioning

confidence: 99%

Molecular Crosstalk Between MYC and HIF in Cancer

Li¹,

Sun²,

Qian

et al. 2020

Front. Cell Dev. Biol.

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The transcription factor c-MYC (MYC thereafter) is a global regulator of gene expression. It is overexpressed or deregulated in human cancers of diverse origins and plays a key role in the development of cancers. Hypoxia-inducible factors (HIFs), a central regulator for cells to adapt to low cellular oxygen levels, is also often overexpressed and activated in many human cancers. HIF mediates the primary transcriptional response of a wide range of genes in response to hypoxia. Earlier studies focused on the inhibition of MYC by HIF during hypoxia, when MYC is expressed at physiological level, to help cells survive under low oxygen conditions. Emerging evidence suggests that MYC and HIF also cooperate to promote cancer cell growth and progression. This review will summarize the current understanding of the complex molecular interplay between MYC and HIF.

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“…In lymphoma, amplification of MYC leads to upregulation of de novo lipogenesis, suggesting it is required for MYC-dependent transformation and growth [8]. MYC cooperates with SREBPs to regulate lipid synthesis and tumor growth in multiple cancer types [9]. Clear cell renal cell carcinomas (ccRCCs), characterized by functional loss of the von Hippel-Lindau (VHL) tumor suppressor that leads to stabilization of the hypoxia inducible factors (HIFs), show a shift in cellular metabolism where glutamine-derived carbon is almost exclusively used for de novo lipogenesis [10].…”

Section: Lipid Metabolism and Cancermentioning

confidence: 99%

Lipid Metabolism at the Nexus of Diet and Tumor Microenvironment

2019

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Obesity is a leading contributing factor to cancer development worldwide. Epidemiological evidence suggests that diet affects cancer risk and also substantially alters therapeutic outcome. Therefore, studying the impact of diet in the development and treatment of cancer should be a clinical priority. In this Review, we set out the evidence supporting the role of lipid metabolism in shaping the tumor microenvironment (TME) and cancer cell phenotype. We will discuss how dietary lipids can impact phenotype thereby affecting disease trajectory and treatment response. Finally, we will posit potential strategies on how this knowledge can be exploited to increase treatment efficacy and patient survival. Obesity and the Tumor Microenvironment Excess caloric intake leads to obesity and is a major risk factor for diabetes, cardiovascular disease, stroke, and incidence of cancer worldwide. Indeed, high body fat is associated with an increased likelihood of developing multiple hematological malignancies, and breast, esophageal, renal, colon, pancreatic, and endometrial cancers [1]. Prospective analysis of 900 000 cancer-free adults in the US showed that men and women with the highest body mass index (BMI) had a 52% and 62% increased risk, respectively, of dying from cancer than their normal weight counterparts [2]. Increased body weight and fat tissue results in altered hormone levels, such as increased estrogen and insulin, which play major roles in cancer development and can result in systemic metabolic changes; that is, hyperglycemia (see Glossary; due to insulin resistance) or elevated levels of circulating lipids. Obesity also promotes tissue inflammation and vascular dysfunction [3]. However, there is limited understanding of the direct impact that diet has on cells within the TME. For example, it is not well known if elevated blood glucose levels promote the proliferation of cancer cells or if increased lipid availability in the TME promotes cancer cells to use these lipids as an energy source or substrates for membrane synthesis. Epidemiological evidence suggests that diet substantially alters treatment outcome in cancer patients; that is, meta-analyses show that breast cancer recurrence is 30% higher in obese women compared to their normal-weight counterparts [4]. Therefore, a better understanding of the effect of diet, in particular the carbohydrate-and fat-rich western diet, on nutrient availability within the TME and its impact on signaling pathways that determine drug sensitivity is essential for the development of novel anticancer therapies. In this Review, we discuss lipid metabolism within the context of the TME and explore how diet can impact cancer phenotype, disease trajectory, and treatment response.

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The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth

Cited by 135 publications

References 113 publications

Regulation of cancer cell metabolism: oncogenic MYC in the driver’s seat

Regulation of cancer cell metabolism: oncogenic MYC in the driver’s seat

Molecular Crosstalk Between MYC and HIF in Cancer

Lipid Metabolism at the Nexus of Diet and Tumor Microenvironment

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