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000287681 1001_ $$00000-0002-9406-6478$$aSainero-Alcolado, Lourdes$$b0
000287681 245__ $$aTargeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma.
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000287681 520__ $$aMetabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.
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000287681 650_7 $$2Other$$aHILPDA
000287681 650_7 $$2Other$$aMYC
000287681 650_7 $$2Other$$aclear cell renal cell carcinoma
000287681 650_7 $$2Other$$aglutamine
000287681 650_7 $$2Other$$alipid droplets
000287681 7001_ $$00009-0001-5321-1253$$aGarde-Lapido, Elisa$$b1
000287681 7001_ $$0P:(DE-He78)7b7131e0870c28d432e48873d295460f$$aSnaebjörnsson, Marteinn Thor$$b2$$udkfz
000287681 7001_ $$aSchoch, Sarah$$b3
000287681 7001_ $$00000-0003-3823-1499$$aStevens, Irene$$b4
000287681 7001_ $$aRuiz-Pérez, María Victoria$$b5
000287681 7001_ $$00000-0003-4647-9769$$aDyrager, Christine$$b6
000287681 7001_ $$aPelechano, Vicent$$b7
000287681 7001_ $$00000-0002-7749-5043$$aAxelson, Håkan$$b8
000287681 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b9$$udkfz
000287681 7001_ $$00000-0001-6376-7792$$aArsenian-Henriksson, Marie$$b10
000287681 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.2310479121$$gVol. 121, no. 7, p. e2310479121$$n7$$pe2310479121$$tProceedings of the National Academy of Sciences of the United States of America$$v121$$x0027-8424$$y2024
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