Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

Sunami, Yoshiaki; Rebelo, Artur; Kleeff, Jörg

doi:10.3390/cancers10010003

Cited by 126 publications

(118 citation statements)

References 131 publications

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“…LGU super-enhancers were uniquely associated with several pathways that include tight junction, Rap1 signaling, and glycerophospholipid metabolism. Aberrant lipid synthesis and the reprogramming of lipid metabolism has been associated with the development and progression of pancreatic cancer [51], and several phospholipids have been identified as potential biomarkers in different types of pancreatic cancers [52,53]. MAPK signaling was the singular KEGG pathway enriched in HGU super-enhancers ( Figure S3).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

et al. 2019

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The spreading of epigenetic domains has emerged as a distinguishing epigenomic phenotype for diverse cell types. In particular, clusters of H3K27ac- and H3K4me3-marked elements, referred to as super-enhancers, and broad H3K4me3 domains, respectively, have been linked to cell identity and disease states. Here, we characterized the broad domains from different pancreatic ductal adenocarcinoma (PDAC) cell lines that represent distinct histological grades. Our integrative genomic analysis found that human derived cell line models for distinct PDAC grades exhibit characteristic broad epigenetic features associated with gene expression patterns that are predictive of patient prognosis and provide insight into pancreatic cancer cell identity. In particular, we find that genes marked by overlapping Low-Grade broad domains correspond to an epithelial phenotype and hold potential as markers for patient stratification. We further utilize ChIP-seq to compare the effects of histone acetyltransferase (HAT) inhibitors to detect global changes in histone acetylation and methylation levels. We found that HAT inhibitors impact certain broad domains of pancreatic cancer cells. Overall, our results reveal potential roles for broad domains in cells from distinct PDAC grades and demonstrate the plasticity of particular broad epigenomic domains to epigenetic inhibitors.

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Section: Discussionmentioning

confidence: 99%

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

et al. 2019

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“…Lipid metabolism is also essential for cancer progression [76]. It not only provides ample building blocks for rapid membrane formation but also produces signaling molecules and substrates for the posttranslational modification of proteins.…”

Section: Lipidsmentioning

confidence: 99%

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

et al. 2020

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Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.

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“…The augmented capacity of PDA cells to either uptake or synthesize lipids and fatty acids (FAs) seems to play an important role in cancer progression. Indeed, high transcriptional levels of FASN or LDLR (cholesterol uptake) are associated with poor overall survival or reoccurrence in PDA respectively [75]. …”

Section: Introductionmentioning

confidence: 99%

“…Indeed, further elucidating mechanisms involved in the regulation and response to different FAs may aid in identifying novel therapeutics and treatment options for patients. Currently, a number of inhibitors targeting lipid metabolism are being evaluated for efficacy in clinical trials in PDA and other cancers [75]. …”

Section: Introductionmentioning

confidence: 99%

The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance

Biancur

Kimmelman

2018

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

107

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Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer that is highly refractory to the current standards of care. The difficulty in treating this disease is due to a number of different factors, including altered metabolism. In PDA, the metabolic rewiring favors anabolic reactions which supply the cancer cell with necessary cellular building blocks for unconstrained growth. Furthermore, PDA cells display high levels of basal autophagy and macropinocytosis. KRAS is the driving oncogene in PDA and many of the metabolic changes are downstream of its activation. Together, these unique pathways for nutrient utilization and acquisition result in metabolic plasticity enabling cells to rapidly adapt to nutrient and oxygen fluctuations. This remarkable adaptability has been implicated as a cause of the intense therapeutic resistance. In this review, we discuss metabolic pathways in PDA tumors and highlight how they contribute to the pathogenesis and treatment of the disease.

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Lipid Metabolism and Lipid Droplets in Pancreatic Cancer and Stellate Cells

Cited by 126 publications

References 131 publications

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

Disruption of Broad Epigenetic Domains in PDAC Cells by HAT Inhibitors

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance

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