Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.

Published online

Journal Article

Enchondroma and chondrosarcoma are the most common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. We performed RNA-seq analysis on chondrocytes from Col2a1Cre;Idh1LSL/+ animals and found that genes implied in cholesterol synthesis pathway were significantly upregulated in the mutant chondrocytes. We examined the phenotypic effect of inhibiting intracellular cholesterol biosynthesis on enchondroma formation by conditionally deleting SCAP (sterol regulatory element-binding protein cleavage-activating protein), a protein activating intracellular cholesterol synthesis, in IDH1 mutant mice. We found fewer enchondromas in animals lacking SCAP. Furthermore, in chondrosarcomas, pharmacological inhibition of intracellular cholesterol synthesis significantly reduced chondrosarcoma cell viability in vitro and suppressed tumor growth in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.

Full Text

Duke Authors

Cited Authors

  • Zhang, H; Wei, Q; Tsushima, H; Puviindran, V; Tang, YJ; Pathmanapan, S; Poon, R; Ramu, E; Al-Jazrawe, M; Wunder, J; Alman, BA

Published Date

  • April 30, 2019

Published In

Volume / Issue

  • 5 /

PubMed ID

  • 31039139

Pubmed Central ID

  • 31039139

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.127232

Language

  • eng

Conference Location

  • United States