TY - JOUR
T1 - Transforming Growth Factor-Beta Signaling in Cancer-Induced Cachexia
T2 - From Molecular Pathways to the Clinics
AU - Balsano, Rita
AU - Kruize, Zita
AU - Lunardi, Martina
AU - Comandatore, Annalisa
AU - Barone, Mara
AU - Cavazzoni, Andrea
AU - Re Cecconi, Andrea David
AU - Morelli, Luca
AU - Wilmink, Hanneke
AU - Tiseo, Marcello
AU - Garajovà, Ingrid
AU - van Zuylen, Lia
AU - Giovannetti, Elisa
AU - Piccirillo, Rosanna
N1 - Funding Information: This research was partly funded by CCA Foundation 2018 Grant (to E.G.), AIRC grant IG-24444 (to E.G.) and AIRC grant IG-19927 (to R.P.), AIRC grant IG-20074 (to M.T.) and KWF Dutch Cancer Society (KWF grant#11957). Publisher Copyright: © 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β). Besides its double-edged role as a tumor suppressor and activator, TGF-β causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-β induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1/GDF15, a member of the TGF-β superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-β is tested as a potential mechanism to revert cachexia, and antibodies against TGF-β reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-β pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-β and such other players could be potential targets for therapy.
AB - Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β). Besides its double-edged role as a tumor suppressor and activator, TGF-β causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-β induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1/GDF15, a member of the TGF-β superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-β is tested as a potential mechanism to revert cachexia, and antibodies against TGF-β reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-β pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-β and such other players could be potential targets for therapy.
KW - TGF-β
KW - cachexia
KW - cancer-related syndrome
UR - http://www.scopus.com/inward/record.url?scp=85137608129&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cells11172671
DO - https://doi.org/10.3390/cells11172671
M3 - Review article
C2 - 36078078
SN - 2073-4409
VL - 11
JO - Cells
JF - Cells
IS - 17
M1 - 2671
ER -