Mechanisms of Cancer Cachexia

Michael J. Tisdale

Research output: Contribution to journalArticle

Abstract

Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the a-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NF?B. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-a, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment. Copyright © 2009 the American Physiological Society
LanguageEnglish
Pages381-410
Number of pages30
JournalPhysiological Reviews
Volume89
Issue number2
DOIs
Publication statusPublished - Apr 2009

Fingerprint

Cachexia
Proteolysis
Skeletal Muscle
Proteasome Endopeptidase Complex
Ubiquitin
Adipose Tissue
Neoplasms
Eukaryotic Small Ribosome Subunits
Peptide Initiation Factors
Muscular Atrophy
Thermogenesis
Lipolysis
Anorexia
Transfer RNA
Lysosomes
Angiotensin II
Protein Kinases
Energy Metabolism
Glucocorticoids
Atrophy

Keywords

  • cancer cachexia
  • cachexia

Cite this

Tisdale, Michael J. / Mechanisms of Cancer Cachexia. In: Physiological Reviews. 2009 ; Vol. 89, No. 2. pp. 381-410.
@article{5537490fcb2f4e8a87f927dac40a90d2,
title = "Mechanisms of Cancer Cachexia",
abstract = "Up to 50{\%} of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the a-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NF?B. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-a, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment. Copyright {\circledC} 2009 the American Physiological Society",
keywords = "cancer cachexia, cachexia",
author = "Tisdale, {Michael J.}",
year = "2009",
month = "4",
doi = "10.1152/physrev.00016.2008",
language = "English",
volume = "89",
pages = "381--410",
journal = "Physiological Reviews",
issn = "0031-9333",
publisher = "American Physiological Society",
number = "2",

}

Mechanisms of Cancer Cachexia. / Tisdale, Michael J.

In: Physiological Reviews, Vol. 89, No. 2, 04.2009, p. 381-410.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mechanisms of Cancer Cachexia

AU - Tisdale, Michael J.

PY - 2009/4

Y1 - 2009/4

N2 - Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the a-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NF?B. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-a, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment. Copyright © 2009 the American Physiological Society

AB - Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body mass. An increased resting energy expenditure is seen, possibly arising from an increased thermogenesis in skeletal muscle due to an increased expression of uncoupling protein, and increased operation of the Cori cycle. Loss of adipose tissue is due to an increased lipolysis by tumor or host products. Loss of skeletal muscle in cachexia results from a depression in protein synthesis combined with an increase in protein degradation. The increase in protein degradation may include both increased activity of the ubiquitin-proteasome pathway and lysosomes. The decrease in protein synthesis is due to a reduced level of the initiation factor 4F, decreased elongation, and decreased binding of methionyl-tRNA to the 40S ribosomal subunit through increased phosphorylation of eIF2 on the a-subunit by activation of the dsRNA-dependent protein kinase, which also increases expression of the ubiquitin-proteasome pathway through activation of NF?B. Tumor factors such as proteolysis-inducing factor and host factors such as tumor necrosis factor-a, angiotensin II, and glucocorticoids can all induce muscle atrophy. Knowledge of the mechanisms of tissue destruction in cachexia should improve methods of treatment. Copyright © 2009 the American Physiological Society

KW - cancer cachexia

KW - cachexia

UR - http://www.scopus.com/inward/record.url?scp=67649982995&partnerID=8YFLogxK

UR - http://physrev.physiology.org/content/89/2/381.full

U2 - 10.1152/physrev.00016.2008

DO - 10.1152/physrev.00016.2008

M3 - Article

VL - 89

SP - 381

EP - 410

JO - Physiological Reviews

T2 - Physiological Reviews

JF - Physiological Reviews

SN - 0031-9333

IS - 2

ER -