Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells
Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells
ABSTRACT We previously described the expression of CD36 and lipoprotein lipase (LPL) by breast cancer (BC) cells and tissues, and the growth-promoting effect of very low-density lipoprotein (VLDL) supplementation observed in BC cell lines only in the presence of LPL. We now describe the deployment of LPL by BC cells. Our data support a model in which LPL is bound to a heparin-like heparan sulfate proteoglycan motif on the BC cell surface and acts in concert with the VLDL receptor to rapidly internalize intact lipoproteins via receptor-mediated endocytosis. We further observe substantial alterations in gene expression programs related to pathways for lipid acquisition (synthesis vs. uptake) in response to each the availability of exogenous triglyceride in tissue culture media and LPL expression status. Current literature emphasizes de novo fatty acid synthesis as the paramount mechanism for lipid acquisition by cancer cells. Our findings indicate that exogenous lipid uptake can serve as an important method of lipid acquisition for cancer cells, alongside de novo lipogenesis, and that the relative reliance on these two modes of lipid acquisition may vary among different BC cell lines and in response to nutrient availability. This concept has obvious implications for the development of therapies aimed at the lipid dependence of many different cancer types. Moreover, the mechanism that we have elucidated provides a direct connection between dietary fat and tumor biology.
Lupien Leslie E.、Bloch Katarzyna、Dehairs Jonas、Wells Wendy A.、Smits Nicole C.、Kinlaw William B.、Feng William W.、Dennis Thea、Swinnen Johannes V.、Kuemmerle Nancy B.、Davis Wilson L.
The Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Program in Experimental and Molecular Medicine, Geisel School of Medicine at DartmouthDepartment of Oncology, LKI ¨C Leuven Cancer InstituteDepartment of Oncology, LKI ¨C Leuven Cancer InstituteThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Pathology and Laboratory Medicine, Geisel School of Medicine at DartmouthThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Microbiology and Immunology, Geisel School of Medicine at DartmouthThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Medicine, Section of Endocrinology and Metabolism, Geisel School of Medicine at DartmouthThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Program in Experimental and Molecular Medicine, Geisel School of Medicine at DartmouthThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Oncology, LKI ¨C Leuven Cancer Institute||Praxis Program, Smith CollegeDepartment of Oncology, LKI ¨C Leuven Cancer InstituteThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Medicine, Section of Hematology and Oncology, White River Junction Veteran?ˉs Administration Medical CenterThe Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center||Department of Medicine, Section of Endocrinology and Metabolism, Geisel School of Medicine at Dartmouth
肿瘤学基础医学生物化学
LPLVLDLRVLDLFASNlipogenesislipoprotein uptakecancer metabolism
Lupien Leslie E.,Bloch Katarzyna,Dehairs Jonas,Wells Wendy A.,Smits Nicole C.,Kinlaw William B.,Feng William W.,Dennis Thea,Swinnen Johannes V.,Kuemmerle Nancy B.,Davis Wilson L..Endocytosis of very low-density lipoprotein particles: an unexpected mechanism for lipid acquisition by breast cancer cells[EB/OL].(2025-03-28)[2025-06-17].https://www.biorxiv.org/content/10.1101/684274.点此复制
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