Dataset Information

Lipid metabolism reprogramming and its potential targets in cancer.

ABSTRACT: Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth. SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor, thus linking glucose metabolism and de novo lipid synthesis. Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.

SUBMITTER: Cheng C

PROVIDER: S-EPMC5993136 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lipid metabolism reprogramming and its potential targets in cancer.

Cheng Chunming C Geng Feng F Cheng Xiang X Guo Deliang D

Cancer communications (London, England) 20180521 1

Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. R ...[more]

PMID: 29784041

Similar Datasets

Project description:BackgroundGlobal DNA methylation alterations are hallmarks of cancer. The tumor-suppressive TET enzymes, which are involved in DNA demethylation, are decreased in prostate cancer (PCa); in particular, TET2 is specifically targeted by androgen-dependent mechanisms of repression in PCa and may play a central role in carcinogenesis. Thus, the identification of key genes targeted by TET2 dysregulation may provide further insight into cancer biology.ResultsUsing a CRISPR/Cas9-derived TET2-knockout prostate cell line, and through whole-transcriptome and whole-methylome sequencing, we identified seven candidate genes-ASB2, ETNK2, MEIS2, NRG1, NTN1, NUDT10, and SRPX-exhibiting reduced expression and increased promoter methylation, a pattern characteristic of tumor suppressors. Decreased expression of these genes significantly discriminates between recurrent and non-recurrent prostate tumors from the Cancer Genome Atlas (TCGA) cohort (n = 423), and ASB2, NUDT10, and SRPX were significantly correlated with lower recurrence-free survival in patients by Kaplan-Meier analysis. ASB2, MEIS2, and SRPX also showed significantly lower expression in high-risk Gleason score 8 tumors as compared to low or intermediate risk tumors, suggesting that these genes may be particularly useful as indicators of PCa progression. Furthermore, methylation array probes in the TCGA dataset, which were proximal to the highly conserved, differentially methylated sites identified in our TET2-knockout cells, were able to significantly distinguish between matched prostate tumor and normal prostate tissues (n = 50 pairs). Except ASB2, all genes exhibited significantly increased methylation at these probes, and methylation status of at least one probe for each of these genes showed association with measures of PCa progression such as recurrence, stage, or Gleason score. Since ASB2 did not have any probes within the TET2-knockout differentially methylated region, we validated ASB2 methylation in an independent series of matched tumor-normal samples (n = 19) by methylation-specific qPCR, which revealed concordant and significant increases in promoter methylation within the TET2-knockout site.ConclusionsOur study identifies seven genes governed by TET2 loss in PCa which exhibit an association between their methylation and expression status and measures of PCa progression. As differential methylation profiles and TET2 expression are associated with advanced PCa, further investigation of these specialized TET2 targets may provide important insights into patterns of carcinogenic gene dysregulation.

Dataset Information

Lipid metabolism reprogramming and its potential targets in cancer.

Publications

Lipid metabolism reprogramming and its potential targets in cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets