DGAT1 Inhibitor Suppresses Prostate Tumor Growth and Migration by Regulating Intracellular Lipids and Non-Centrosomal MTOC Protein GM130

Scientific Reports
Francesca NardiSusan E Crawford

Abstract

Acyl-CoA:diacylglycerol acyltransferase I (DGAT1) is a key enzyme in lipogenesis which is increased in metabolically active cells to meet nutrient requirements. DGAT1 has been recognized as an anti-obesity target; however, its role in the tumor microenvironment remains unclear. We postulated that, in prostate cancer (PCa) cells, augmented lipogenesis and growth are due to increased DGAT1 expression leading to microtubule-organizing center (MTOC) amplification. Thus, therapeutic targeting of DGAT1 potentially has tumor suppressive activity. We tested whether blocking DGAT1 in PCa cells altered MTOC and lipid signaling. Western blot and immunofluorescence were performed for MTOC and triglyceride mediators. Treatment with a DGAT1 inhibitor was evaluated. We found a stepwise increase in DGAT1 protein levels when comparing normal prostate epithelial cells to PCa cells, LNCaP and PC-3. Lipid droplets, MTOCs, and microtubule-regulating proteins were reduced in tumor cells treated with a DGAT1 inhibitor. Depletion of the non-centrosomal MTOC protein GM130 reduced PCa cell proliferation and migration. Inhibition of DGAT1 reduced tumor growth both in vitro and in vivo, and a negative feedback loop was discovered between DGAT1, PEDF, and ...Continue Reading

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Citations

Feb 8, 2020·Cell Death & Disease·André L S CruzPatricia T Bozza
Jan 8, 2020·Contact·Marcus D Kilwein, M A Welte
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Aug 14, 2021·Frontiers in Oncology·Natalia ScagliaGiorgia Zadra

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
biosensor
Protein Assay
confocal microscopy
transfection

Software Mentioned

Image J
ImageJ
Element
NIS
GraphPad Prism
Filament Sensor

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