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Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.

Publication ,  Journal Article
Kir, S; White, JP; Kleiner, S; Kazak, L; Cohen, P; Baracos, VE; Spiegelman, BM
Published in: Nature
September 4, 2014

Cachexia is a wasting disorder of adipose and skeletal muscle tissues that leads to profound weight loss and frailty. About half of all cancer patients suffer from cachexia, which impairs quality of life, limits cancer therapy and decreases survival. One key characteristic of cachexia is higher resting energy expenditure levels than in healthy individuals, which has been linked to greater thermogenesis by brown fat. How tumours induce brown fat activity is unknown. Here, using a Lewis lung carcinoma model of cancer cachexia, we show that tumour-derived parathyroid-hormone-related protein (PTHrP) has an important role in wasting, through driving the expression of genes involved in thermogenesis in adipose tissues. Neutralization of PTHrP in tumour-bearing mice blocked adipose tissue browning and the loss of muscle mass and strength. Our results demonstrate that PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia. Thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 4, 2014

Volume

513

Issue

7516

Start / End Page

100 / 104

Location

England

Related Subject Headings

  • Thermogenesis
  • Parathyroid Hormone-Related Protein
  • Organ Size
  • Muscle, Skeletal
  • Mice
  • Male
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Energy Metabolism
 

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Kir, S., White, J. P., Kleiner, S., Kazak, L., Cohen, P., Baracos, V. E., & Spiegelman, B. M. (2014). Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature, 513(7516), 100–104. https://doi.org/10.1038/nature13528
Kir, Serkan, James P. White, Sandra Kleiner, Lawrence Kazak, Paul Cohen, Vickie E. Baracos, and Bruce M. Spiegelman. “Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.Nature 513, no. 7516 (September 4, 2014): 100–104. https://doi.org/10.1038/nature13528.
Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 2014 Sep 4;513(7516):100–4.
Kir, Serkan, et al. “Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.Nature, vol. 513, no. 7516, Sept. 2014, pp. 100–04. Pubmed, doi:10.1038/nature13528.
Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, Spiegelman BM. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 2014 Sep 4;513(7516):100–104.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

September 4, 2014

Volume

513

Issue

7516

Start / End Page

100 / 104

Location

England

Related Subject Headings

  • Thermogenesis
  • Parathyroid Hormone-Related Protein
  • Organ Size
  • Muscle, Skeletal
  • Mice
  • Male
  • Humans
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
  • Energy Metabolism