PMID- 32055677
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2372-7705 (Print)
IS  - 2372-7705 (Electronic)
IS  - 2372-7705 (Linking)
VI  - 16
DP  - 2020 Mar 27
TI  - Wnt7a Counteracts Cancer Cachexia.
PG  - 134-146
LID - 10.1016/j.omto.2019.12.011 [doi]
AB  - Cancer cachexia is a complex metabolic disease so far lacking effective therapy, 
      and it accounts for approximately one third of all cancer-related deaths 
      worldwide. The extracellular ligand Wnt7a has a dual function in skeletal muscle, 
      inducing the anabolic AKT/mammalian target of rapamycin (mTOR) pathway in 
      myofibers and driving muscle stem cell expansion in skeletal muscle, making it a 
      promising candidate for treatment of muscle wasting diseases. In murine and human 
      myotubes, Wnt7a activates the anabolic AKT/mTOR pathway, thereby preventing 
      cachexia-induced atrophy with a single application being sufficient to prevent 
      atrophy independently of the tumor cell type causing cachexia. Addition of Wnt7a 
      also improved activation and differentiation of muscle stem cells in cancer 
      cachexia, a condition under which skeletal muscle regeneration is severely 
      impaired due to stalled muscle stem cell differentiation. Finally, we show that 
      Wnt7a prevents cancer cachexia in an in vivo mouse model based on C26 colon 
      carcinoma cells. Wnt7a has a dual role in cachectic skeletal muscle; that is, it 
      effectively counteracts muscle wasting through activation of the anabolic 
      AKT/mTOR pathway and, furthermore, reverts the loss of muscle stem cell 
      functionality due to cancer cachexia, making Wnt7a a promising candidate for an 
      ameliorative treatment of cancer cachexia.
CI  - (c) 2020 The Author(s).
FAU - Schmidt, Manuel
AU  - Schmidt M
AD  - Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 
      Jena, Germany.
FAU - Poser, Christine
AU  - Poser C
AD  - Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 
      Jena, Germany.
FAU - von Maltzahn, Julia
AU  - von Maltzahn J
AD  - Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 
      Jena, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200111
PL  - United States
TA  - Mol Ther Oncolytics
JT  - Molecular therapy oncolytics
JID - 101666776
PMC - PMC7005483
OTO - NOTNLM
OT  - Wnt7a
OT  - atrophy
OT  - cancer cachexia
OT  - muscle stem cell
OT  - muscle wasting
OT  - satellite cell
OT  - skeletal muscle
EDAT- 2020/02/15 06:00
MHDA- 2020/02/15 06:01
PMCR- 2020/01/11
CRDT- 2020/02/15 06:00
PHST- 2019/08/10 00:00 [received]
PHST- 2019/12/23 00:00 [accepted]
PHST- 2020/02/15 06:00 [entrez]
PHST- 2020/02/15 06:00 [pubmed]
PHST- 2020/02/15 06:01 [medline]
PHST- 2020/01/11 00:00 [pmc-release]
AID - S2372-7705(20)30003-6 [pii]
AID - 10.1016/j.omto.2019.12.011 [doi]
PST - epublish
SO  - Mol Ther Oncolytics. 2020 Jan 11;16:134-146. doi: 10.1016/j.omto.2019.12.011. 
      eCollection 2020 Mar 27.