Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

Son, Bong Soo; Lee, Sung-Min; Kim, Hyun Woo; Kang, Hyunkoo; Jeon, Jaewan; Jo, Sunmi; Seong, Ki Moon; Lee, Su Jae; Youn, Hye Sook; Youn, Bu Hyun

doi:10.1038/s41388-019-0974-4

Cited by 32 publications

(34 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Decreased gluconeogenesis is a phenomenon often related to increased glycolytic activity and loss of a key gluconeogenesis regulator FBP1 has previously been shown to induce glycolysis, and lead to hyperglycemia and lactic acidosis [26,101,102]. FBP1 downregulation has also been found to reduce ROS production and to be associated with EMT [26,103,104]. Further, in line with downregulated gluconeogenesis, we nd a panel of genes involved in fatty acid oxidation (FAO) to be decreased in tumor samples compared to NSCLC tissue.…”

Section: Discussionsupporting

confidence: 54%

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Dyrstad¹,

Lotsberg²,

Tan³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Non-small cell lung cancer (NSCLC) patients harboring oncogenic mutations in the epidermal growth factor receptor (EGFR) inevitably develop resistance to targeted therapy. Drug resistance is an example of cancer cell plasticity where cells change according to diverse microenvironmental pressure, which can be described as a way of evolution by natural selection. Metabolic rewiring during cancer development may support several malignant features and facilitate emergence of therapy resistant clones. Results Analysis of transcriptome data from two independent NSLSC patient cohorts identified upregulated markers of glucose metabolism and ROS defense in tumors compared to normal tissue. We show that these alterations were associated with increased expression of pyruvate dehydrogenase kinase 1 (PDK1). We established relevant in vitro models to study metabolic alterations in the context of resistance to EGFR TKIs to determine if targeted metabolic intervention would prevent development of resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) in NSCLC cells. The PDK inhibitor dichloroacetate (DCA) was shown to reduce cell growth. This mechanism was associated with redirected metabolism towards pyruvate and lactate oxidation, and reduced lactate production, both in EGFR TKI sensitive and resistant NSCLC cells. Conclusion We propose that the intracellular stress created by redirecting pyruvate metabolism can prevent EGFR TKI resistance in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 54%

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Dyrstad¹,

Lotsberg²,

Tan³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…It is also interesting that ectopic overexpression of FBP1 in the SNAIL1-overexpressing cell lines inhibited the initiation of EMT and abrogated the downregulation of E-cadherin that is required for EMT (212). Downregulation of FBP1 has been shown to be a poor prognostic factor in gastric cancer (213) and in aggressive glioblastomas (214), as well indicating the importance of this finding.…”

Section: Glycolysismentioning

confidence: 95%

EMT Factors and Metabolic Pathways in Cancer

Georgakopoulos-Soares

et al. 2020

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) represents a biological program during which epithelial cells lose their cell identity and acquire a mesenchymal phenotype. EMT is normally observed during organismal development, wound healing and tissue fibrosis. However, this process can be hijacked by cancer cells and is often associated with resistance to apoptosis, acquisition of tissue invasiveness, cancer stem cell characteristics, and cancer treatment resistance. It is becoming evident that EMT is a complex, multifactorial spectrum, often involving episodic, transient or partial events. Multiple factors have been causally implicated in EMT including transcription factors (e.g., SNAIL, TWIST, ZEB), epigenetic modifications, microRNAs (e.g., miR-200 family) and more recently, long non-coding RNAs. However, the relevance of metabolic pathways in EMT is only recently being recognized. Importantly, alterations in key metabolic pathways affect cancer development and progression. In this review, we report the roles of key EMT factors and describe their interactions and interconnectedness. We introduce metabolic pathways that are involved in EMT, including glycolysis, the TCA cycle, lipid and amino acid metabolism, and characterize the relationship between EMT factors and cancer metabolism. Finally, we present therapeutic opportunities involving EMT, with particular focus on cancer metabolic pathways.

show abstract

“…For mRNA expression assessment, qRT-PCR was performed following the previous study [ 23 ]. Briefly, RNA was isolated with TRIzol following the manufacturers’ instructions and real-time qRT-PCR was performed using an Applied Biosystems StepOne Real-Time PCR System (Applied Biosystems, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

Lee

Youn

2020

Nutrients

Self Cite

View full text Add to dashboard Cite

Hyperlipidemia, a syndrome characterized by an abnormal elevation of blood lipids, causes chronic lethal metabolic disorders. Although statins are regularly prescribed to patients, an alternative to treat the burden of excessive lipids is required for cholesterol control. In this study, it was found that the treatment of casein hydrolyzed by pepsin and trypsin induced trans-intestinal cholesterol excretion (TICE) through ATP-binding cassette subfamily G members 5 (ABCG5) expression. Next, we analyzed sequences of the peptides responsible for TICE induction, synthesized artificial peptides based on the sequences, and the hypolipidemic effects of the peptide treatments were assessed in both in vitro and in vivo models. We determined that two bioactive peptides contained in casein hydrolysates (SQSKVLPVPQK and HPHPHLSF) induced TICE through the expression of ABCG5 in enterocytes and suppressed hepatic mRNA expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1by ileal FGF19 expression both in an liver X receptor α (LXRα)-mediated manner. In the hyperlipidemic mouse models, the oral administration of peptides reduced serum cholesterol levels through elevation of the ABCG5 expression in proximal intestine and fecal cholesterol secretion. Besides this, peptides induced ileal expression of fibroblast growth factor 15/19 (FGF15/19) and inhibited hepatic bile acid synthesis. We found that the oral treatment of casein-derived bioactive peptides could improve hyperlipidemia by regulating intestinal excretion and hepatic synthesis of cholesterols.

show abstract

Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

Cited by 32 publications

References 53 publications

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

Inhibition of pyruvate dehydrogenase kinase redirects NSCLC cell metabolism and counteracts development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors

EMT Factors and Metabolic Pathways in Cancer

Hypolipidemic Roles of Casein-Derived Peptides by Regulation of Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis

Contact Info

Product

Resources

About