Dataset Information

Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.

ABSTRACT: The known link between obesity and cancer suggests an important interaction between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that tumor development influences the host lipid metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and low-density lipoprotein (LDL) turnover. To assess whether tumor progression was dependent on tumor-induced hyperlipidemia, we utilized the VLDL production-deficient mouse model, carboxylesterase3/triacylglycerol hydrolase (Ces3/TGH) knockout mice. In Ces3/Tgh(-/-) tumor-bearing mice, plasma triglyceride and cholesterol levels were attenuated. Importantly tumor weight was reduced in Ces3/Tgh(-/-) mice. Mechanistically, reduced tumor growth in Ces3/Tgh(-/-) mice was attributed to reversal of tumor-induced PCSK9-mediated degradation of hepatic LDLR and decrease of LDL turnover. Our data demonstrate that tumor-induced hyperlipidemia encompasses a feed-forward loop that reprograms hepatic lipoprotein homeostasis in part by providing LDL cholesterol to support tumor growth.

SUBMITTER: Huang J

PROVIDER: S-EPMC4984953 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.

Huang Jianfeng J Li Lena L Lian Jihong J Schauer Silvia S Vesely Paul W PW Kratky Dagmar D Hoefler Gerald G Lehner Richard R

Cell reports 20160331 2

The known link between obesity and cancer suggests an important interaction between the host lipid metabolism and tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that tumor development influences the host lipid metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production and blunting VLDL and low-density lipoprotein (LDL) turnover. To assess whether tumor progression was dependent on tumor-i ...[more]

PMID: 27050512

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Project description:Simple Summary The APOBEC3 family (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like) was shown to induce tumor mutations through an aberrant DNA editing mechanism. In this study, we found that APOBEC genes were widely and significantly differentially expressed between normal and cancer samples in 16 cancer types, and their expression levels were significantly correlated with the prognostic value in 17 cancer types. Further analysis of the APOBEC family revealed extensive regulatory mechanisms by which they affect the tumor microenvironment, the process of tumor oncogenesis and development, and their association with patient prognosis in pan-cancer. Abstract The accumulating evidence demonstrates that the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC), DNA-editing protein plays an important role in the molecular pathogenesis of cancer. In particular, the APOBEC3 family was shown to induce tumor mutations by an aberrant DNA editing mechanism. However, knowledge regarding the reconstitution of the APOBEC family genes across cancer types is still lacking. Here, we systematically analyzed the molecular alterations, immuno-oncological features, and clinical relevance of the APOBEC family in pan-cancer. We found that APOBEC genes were widely and significantly differentially expressed between normal and cancer samples in 16 cancer types, and that their expression levels are significantly correlated with the prognostic value in 17 cancer types. Moreover, two patterns of APOBEC-mediated stratification with distinct immune characteristics were identified in different cancer types, respectively. In ACC, for example, the first pattern of APOBEC-mediated stratification was closely correlated with the phenotype of immune activation, which was characterized by a high immune score, increased infiltration of CD8 T cells, and higher survival. The other pattern of APOBEC-mediated stratification was closely correlated with the low-infiltration immune phenotype, which was characterized by a low immune score, lack of effective immune infiltration, and poorer survival. Further, we found the APOBEC-mediated pattern with low-infiltration immune was also highly associated with the advanced tumor subtype and the CIMP-high tumor subtype (CpG island hypermethylation). Patients with the APOBEC-mediated pattern with immune activation were more likely to have therapeutic advantages in ICB (immunological checkpoint blockade) treatment. Overall, our results provide a valuable resource that will be useful in guiding oncologic and therapeutic analyses of the role of APOBEC family in cancer.

Dataset Information

Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.

Publications

Tumor-Induced Hyperlipidemia Contributes to Tumor Growth.

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