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Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.

Publication ,  Journal Article
Pathmanapan, S; Poon, R; De Renshaw, TB; Nadesan, P; Nakagawa, M; Seesankar, GA; Ho Loe, AK; Zhang, HH; Guinovart, JJ; Duran, J; Newgard, CB ...
Published in: Cell Rep
June 27, 2023

Chondrosarcomas are the most common malignancy of cartilage and are associated with somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes. Somatic IDH mutations are also found in its benign precursor lesion, enchondromas, suggesting that IDH mutations are early events in malignant transformation. Human mutant IDH chondrosarcomas and mutant Idh mice that develop enchondromas investigated in our studies display glycogen deposition exclusively in mutant cells from IDH mutant chondrosarcomas and Idh1 mutant murine growth plates. Pharmacologic blockade of glycogen utilization induces changes in tumor cell behavior, downstream energetic pathways, and tumor burden in vitro and in vivo. Mutant IDH1 interacts with hypoxia-inducible factor 1α (HIF1α) to regulate expression of key enzymes in glycogen metabolism. Here, we show a critical role for glycogen in enchondromas and chondrosarcomas, which is likely mediated through an interaction with mutant IDH1 and HIF1α.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 27, 2023

Volume

42

Issue

6

Start / End Page

112578

Location

United States

Related Subject Headings

  • Mutation
  • Mice
  • Isocitrate Dehydrogenase
  • Humans
  • Chondrosarcoma
  • Chondroma
  • Cartilage
  • Bone Neoplasms
  • Animals
  • 31 Biological sciences
 

Citation

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Pathmanapan, S., Poon, R., De Renshaw, T. B., Nadesan, P., Nakagawa, M., Seesankar, G. A., … Alman, B. A. (2023). Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation. Cell Rep, 42(6), 112578. https://doi.org/10.1016/j.celrep.2023.112578
Pathmanapan, Sinthu, Raymond Poon, Tomasa Barrientos De Renshaw, Puviindran Nadesan, Makoto Nakagawa, Gireesh A. Seesankar, Adrian Kwan Ho Loe, et al. “Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.Cell Rep 42, no. 6 (June 27, 2023): 112578. https://doi.org/10.1016/j.celrep.2023.112578.
Pathmanapan S, Poon R, De Renshaw TB, Nadesan P, Nakagawa M, Seesankar GA, et al. Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation. Cell Rep. 2023 Jun 27;42(6):112578.
Pathmanapan, Sinthu, et al. “Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.Cell Rep, vol. 42, no. 6, June 2023, p. 112578. Pubmed, doi:10.1016/j.celrep.2023.112578.
Pathmanapan S, Poon R, De Renshaw TB, Nadesan P, Nakagawa M, Seesankar GA, Ho Loe AK, Zhang HH, Guinovart JJ, Duran J, Newgard CB, Wunder JS, Alman BA. Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation. Cell Rep. 2023 Jun 27;42(6):112578.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

June 27, 2023

Volume

42

Issue

6

Start / End Page

112578

Location

United States

Related Subject Headings

  • Mutation
  • Mice
  • Isocitrate Dehydrogenase
  • Humans
  • Chondrosarcoma
  • Chondroma
  • Cartilage
  • Bone Neoplasms
  • Animals
  • 31 Biological sciences