Transforming Growth Factor-Beta Signaling in Cancer-Induced Cachexia: From Molecular Pathways to the Clinics.
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| Abstract |
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.
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| Authors | Rita Balsano, Zita Kruize, Martina Lunardi, Annalisa Comandatore, Mara Barone, Andrea Cavazzoni, Andrea David Re Cecconi, Luca Morelli, Hanneke Wilmink, Marcello Tiseo, Ingrid Garajovà, Lia van Zuylen, Elisa Giovannetti, Rosanna Piccirillo |
| Journal | Cells (Cells) Vol. 11 Issue 17 (08 28 2022) ISSN: 2073-4409 [Electronic] Switzerland |
| PMID | 36078078 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't) |
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