| First Author | Huang J | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 2 | Pages | 336-48 |
| PubMed ID | 27050512 | Mgi Jnum | J:234948 |
| Mgi Id | MGI:5792469 | Doi | 10.1016/j.celrep.2016.03.020 |
| Citation | Huang J, et al. (2016) Tumor-Induced Hyperlipidemia Contributes to Tumor Growth. Cell Rep 15(2):336-48 |
| abstractText | 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. |
