Myc linked to dysregulation of cholesterol transport and storage in nonsmall cell lung cancer

Hall, Zoe; Wilson, Catherine H.; Burkhart, Deborah L.; Ashmore, Tom; Evan, Gérard I.; Griffin, Julian L.

doi:10.1194/jlr.ra120000899

Cited by 15 publications

(12 citation statements)

References 58 publications

(46 reference statements)

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“…Consistently, OLR1 activation plays an important role in the pathogenesis of different cancers particularly pancreatic cancer. 194 , 195 OLR1, through upregulation of c-Myc, can promote pancreatic cancer cells proliferation, metastasis, and chemoresistance to gemcitabine. OLR1 is overexpressed in pancreatic cancer.…”

Section: The Effect Of C-myc On Cancer Cells Metabolismmentioning

confidence: 99%

Target c-Myc to treat pancreatic cancer

Ala

2022

Cancer Biology & Therapy

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C-Myc overexpression is a common finding in pancreatic cancer and predicts the aggressive behavior of cancer cells. It binds to the promoter of different genes, thereby regulating their transcription. C-Myc is downstream of KRAS and interacts with several oncogenic and proliferative pathways in pancreatic cancer. C-Myc enhances aerobic glycolysis in cancer cells and regulates glutamate biosynthesis from glutamine. It provides enough energy for cancer cells’ metabolism and sufficient substrate for the synthesis of organic molecules. C-Myc overexpression is associated with chemoresistance, intra-tumor angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis in pancreatic cancer. Despite its title, c-Myc is not “undruggable” and recent studies unveiled that it can be targeted, directly or indirectly. Small molecules that accelerate c-Myc ubiquitination and degradation have been effective in preclinical studies. Small molecules that hinder c-Myc-MAX heterodimerization or c-Myc/MAX/DNA complex formation can functionally inhibit c-Myc. In addition, c-Myc can be targeted through transcriptional, post-transcriptional, and translational modifications.

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Section: The Effect Of C-myc On Cancer Cells Metabolismmentioning

confidence: 99%

Target c-Myc to treat pancreatic cancer

Ala

2022

Cancer Biology & Therapy

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“…Cholesterol is normally synthesized from acetyl-CoA. Recent studies have found that cholesterol exerts an immunosuppressive TME by promoting the expression of immune checkpoint on CD8 + T cells, which induces ER stress and consequently exhaustion of those T cells [96,97] . In KRAS-driven NSCLC, the synthesis of cholesterol has been found to be induced by Myc proto-oncogene protein (MYC) activation.…”

Section: Lipid Metabolismmentioning

confidence: 99%

Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Li¹,

Hu²,

Peng³

et al. 2022

CDR

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Non-small cell lung cancer (NSCLC) patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation are associated with significant clinical heterogeneity and a poor prognosis to standard NSCLC therapies such as surgical resection, radiotherapy, chemotherapies, and targeted medicines. However, the application of immune checkpoints inhibitors (ICIs) has dramatically altered the therapeutic pattern of NSCLC management. Clinical studies have indicated that some KRAS-mutant NSCLC patients could benefit from ICIs; however, the responses in some patients are still poor. This review intends to elucidate the mechanisms of resistance to immunotherapy in KRAS-driven NSCLC and highlight the TME functions altered by immunoinhibitors, immunostimulators, and cancer metabolism. These metabolic pathways could potentially be promising approaches to overcome immunotherapy resistance.

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“…In fact, increased myc activity reduced the efflux of cholesterol while enhancing its influx and the accumulation of cholesteryl esters in LDs. This mechanism was proposed to contribute to the growth of KRAS, myc-overexpressing NSCLC cancers, suggesting that targeting cholesterol metabolism may be explored as a novel approach for lung cancer treatment with diagnostic and stratification potential [84].…”

Section: Cholesterol Metabolismmentioning

confidence: 99%

Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer

Eltayeb

Monica

Tiseo

et al. 2022

Cells

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Lung cancer is the leading cause of cancer deaths worldwide. Most of lung cancer cases are classified as non-small cell lung cancers (NSCLC). EGFR has become an important therapeutic target for the treatment of NSCLC patients, and inhibitors targeting the kinase domain of EGFR are currently used in clinical settings. Recently, an increasing interest has emerged toward understanding the mechanisms and biological consequences associated with lipid reprogramming in cancer. Increased uptake, synthesis, oxidation, or storage of lipids has been demonstrated to contribute to the growth of many types of cancer, including lung cancer. In this review, we provide an overview of metabolism in cancer and then explore in more detail the role of lipid metabolic reprogramming in lung cancer development and progression and in resistance to therapies, emphasizing its connection with EGFR signaling. In addition, we summarize the potential therapeutic approaches targeting lipid metabolism for lung cancer treatment.

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Myc linked to dysregulation of cholesterol transport and storage in nonsmall cell lung cancer

Cited by 15 publications

References 58 publications

Target c-Myc to treat pancreatic cancer

Target c-Myc to treat pancreatic cancer

Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer

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